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    Clinical Trial Results:
    A 12-week, multicenter, randomized, double-blind, double-dummy, 2-arm parallel group study comparing the efficacy and safety of Foster® NEXThaler® (beclomethasone dipropionate 100 µg plus formoterol 6 µg/actuation), 2 inhalations b.i.d., versus Seretide® Accuhaler® (fluticasone 250 µg plus salmeterol 50 µg/actuation), 1 inhalation b.i.d., on small airway derived parameters in patients with asthma.

    Summary
    EudraCT number
    		 2011-003449-17
    Trial protocol
    		 IT  
    Global end of trial date
    24 Feb 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Jul 2016
    First version publication date
    09 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MC-PR-15009-001-11
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01570478
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Chiesi Farmaceutici S.p.A.
    Sponsor organisation address
    Via Palermo 26/A, Parma, Italy, 43122
    Public contact
    Clinical Trial Transparency Manager, Chiesi Farmaceutici S.p.A., ClinicalTrials_info@chiesi.com
    Scientific contact
    Clinical Trial Transparency Manager, Chiesi Farmaceutici S.p.A., ClinicalTrials_info@chiesi.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 Feb 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Feb 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Feb 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the higher efficacy of Foster® NEXThaler® 100/6 extra fine (two inhalations b.i.d.) versus Seretide® Accuhaler® 250/50 (one inhalation b.i.d.), in terms of pulmonary function (change from baseline to the end of treatment in post-dose peripheral airway resistance) in patients with asthma.
    Protection of trial subjects
    The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines and local law requirements. Other than routine care, no specific measures for protection of trial subjects were implemented.
    Background therapy
    		 After a pre-screening visit (Visit 0 at week -5 before the randomization visit) and a screening visit (Visit 1 at week -4), the study plan foresees a 4-week run-in period where patients will receive a standardised treatment with Seretide® Accuhaler® 250/50 μg, 1 inhalation b.i.d. (daily dose of FP 500 μg plus SALM 100 μg) and have any non-permitted medications withdrawn prior to entry into test treatment period.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Jul 2012
    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
    Italy: 108
    Worldwide total number of subjects
    108
    EEA total number of subjects
    108
    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)
    108
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 149 patients were screened and 41 of them were not randomised, mainly for ineligibility. Therefore, 108 patients in total were randomised to receive the assigned treatment: 54 were assigned to the Foster® NEXThaler® group (Foster®) and 54 were assigned to the Seretide® Accuhaler® group (Seretide®).

    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
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The realization of the double-blind design was made possible by the use of a Foster® NEXThaler® and Seretide® Accuhaler® placebo, which was totally indistinguishable from the respective active in terms of size, shape, colour and mode of inhalation. Each placebo was administered together with the alternate active ingredient (p.28 CSR).

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Test treatment
    Arm description
    		 Foster® NEXThaler® (beclomethasone dipropionate 100 μg plus formoterol 6 μg per actuation), 2 inhalations b.i.d. (daily dose of BDP 400 μg plus FF 24 μg) plus Seretide® Accuhaler® placebo, 1 inhalation b.i.d.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Foster® NEXThaler®
    Investigational medicinal product code
    Other name
    BDP /FF NEXThaler, beclomethasone dipropionate, formoterol fumarate
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Foster® NEXThaler® (beclomethasone dipropionate 100 μg plus formoterol 6 μg per actuation), 2 inhalations b.i.d. (daily dose of BDP 400 μg plus FF 24 μg) plus Seretide® Accuhaler® placebo, 1 inhalation b.i.d.

    Arm title
    		 Reference treatment
    Arm description
    		 Seretide Accuhaler: fixed combination of fluticasone propionate 250 μg plus salmeterol xinafoate 50 μg per actuation. (daily dose of FP 500 µg plus SX 100 µg) plus Foster® NEXThaler® placebo, 2 inhalations b.i.d.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Seretide® Accuhaler
    Investigational medicinal product code
    Other name
    fluticasone propionate, salmeterol xinafoate
    Pharmaceutical forms
    Inhalation powder, pre-dispensed
    Routes of administration
    Inhalation use
    Dosage and administration details
    Seretide® Accuhaler® (fluticasone propionate 250 μg plus salmeterol xinafoate 50 μg per actuation), 1 inhalation b.i.d. (daily dose of fluticasone 500 μg plus salmeterol 100 μg) plus Foster® NEXThaler® placebo, 2 inhalations b.i.d.

    Number of subjects in period 1
    		Test treatment Reference treatment
    Started
    54
    54
    Completed
    49
    46
    Not completed
    5
    8
         Consent withdrawn by subject
    3
    6
         Inclusion/exclusion criteria not met
    -
    2
         Adverse event, non-fatal
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Test treatment
    Reporting group description
    		 Foster® NEXThaler® (beclomethasone dipropionate 100 μg plus formoterol 6 μg per actuation), 2 inhalations b.i.d. (daily dose of BDP 400 μg plus FF 24 μg) plus Seretide® Accuhaler® placebo, 1 inhalation b.i.d.

    Reporting group title
    Reference treatment
    Reporting group description
    		 Seretide Accuhaler: fixed combination of fluticasone propionate 250 μg plus salmeterol xinafoate 50 μg per actuation. (daily dose of FP 500 µg plus SX 100 µg) plus Foster® NEXThaler® placebo, 2 inhalations b.i.d.

    Reporting group values
    		 Test treatment Reference treatment Total
    Number of subjects
    		 54 54 108
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 54 54 108
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.2 ( 15.7 ) 51 ( 16.1 ) -
    Gender categorical
    Units: Subjects
        Female
    		 13 19 32
        Male
    		 41 35 76
    Subject analysis sets

    Subject analysis set title
    ITT Population - Test treatment
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who receive at least one administration of the study medication and with at least one available postbaseline efficacy evaluation

    Subject analysis set title
    ITT Population - Reference treatment
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who receive at least one administration of the study medication and with at least one available postbaseline efficacy evaluation

    Subject analysis set title
    Safety population - Test treatment
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized patients who received at least one administration of the study medication.

    Subject analysis set title
    safety population - Reference treatment
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized patients who received at least one administration of the study medication.

    Subject analysis sets values
    		 ITT Population - Test treatment ITT Population - Reference treatment Safety population - Test treatment safety population - Reference treatment
    Number of subjects
    54
    54
    54
    54
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    50.2 ( 15.7 )
    51 ( 16.1 )
    50.2 ( 15.7 )
    51 ( 16.1 )
    Gender categorical
    Units: Subjects
        Female
    13
    19
    13
    19
        Male
    41
    35
    41
    35

    End points

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    End points reporting groups
    Reporting group title
    Test treatment
    Reporting group description
    		 Foster® NEXThaler® (beclomethasone dipropionate 100 μg plus formoterol 6 μg per actuation), 2 inhalations b.i.d. (daily dose of BDP 400 μg plus FF 24 μg) plus Seretide® Accuhaler® placebo, 1 inhalation b.i.d.

    Reporting group title
    Reference treatment
    Reporting group description
    		 Seretide Accuhaler: fixed combination of fluticasone propionate 250 μg plus salmeterol xinafoate 50 μg per actuation. (daily dose of FP 500 µg plus SX 100 µg) plus Foster® NEXThaler® placebo, 2 inhalations b.i.d.

    Subject analysis set title
    ITT Population - Test treatment
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who receive at least one administration of the study medication and with at least one available postbaseline efficacy evaluation

    Subject analysis set title
    ITT Population - Reference treatment
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who receive at least one administration of the study medication and with at least one available postbaseline efficacy evaluation

    Subject analysis set title
    Safety population - Test treatment
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized patients who received at least one administration of the study medication.

    Subject analysis set title
    safety population - Reference treatment
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized patients who received at least one administration of the study medication.

    Primary: Change from baseline to end of treatment in post-dose peripheral airway resistance [R(5Hz) - R(20Hz)]

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    End point title
    		 Change from baseline to end of treatment in post-dose peripheral airway resistance [R(5Hz) - R(20Hz)]
    End point description
    Peripheral airway resistance (R5-R20) was measured by Impulse Oscillometry as the difference between total airway resistance (R5) and central airway resistance (R20)
    End point type
    Primary
    End point timeframe
    From Vist 1 to Visit 5 (week 12)
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.06 ( 0.085 )
    -0.064 ( 0.081 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.928
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.025
         upper limit
    		 0.027

    Secondary: Changes from baseline at each clinic visit in pre-dose R5 (total airway resistance)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose R5 (total airway resistance)
    End point description
    Total airway resistance (R5) was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit, from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.029 ( 0.124 )
    -0.051 ( 0.143 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.53
    Method
    		 Mixed models analysis
    Parameter type
    		 Median difference (net)
    Point estimate
    0.016
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.034
         upper limit
    		 0.065

    Secondary: Changes from baseline at each clinic visit in post-dose R5 (total airway resistance)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose R5 (total airway resistance)
    End point description
    Total airway resistance (R5) was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.1 ( 0.124 )
    -0.098 ( 0.117 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.783
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.006
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.049
         upper limit
    		 0.037

    Secondary: Changes from baseline at each clinic visit in pre-dose R20 (central airway resistance)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose R20 (central airway resistance)
    End point description
    Central airway resistance (R20) was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.008 ( 0.064 )
    -0.021 ( 0.071 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.444
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.016
         upper limit
    		 0.035

    Secondary: Changes from baseline at each clinic visit in post-dose R20 (central airway resistance)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose R20 (central airway resistance)
    End point description
    Central airway resistance (R20) was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.04 ( 0.071 )
    -0.035 ( 0.057 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.55
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.007
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.032
         upper limit
    		 0.017

    Secondary: Changes from baseline at each clinic visit in pre-dose R5 - R20 (peripheral airway resistance)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose R5 - R20 (peripheral airway resistance)
    End point description
    Peripheral airway resistance (R5-R20) was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.021 ( 0.094 )
    -0.03 ( 0.098 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.745
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.006
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.029
         upper limit
    		 0.04

    Secondary: Changes from baseline at each clinic visit in post-dose R5 - R20 (peripheral airway resistance)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose R5 - R20 (peripheral airway resistance)
    End point description
    Peripheral airway resistance (R5 - R20) was measured by Impulse Oscillometry. Only data from Visit 4 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.072 ( 0.075 )
    -0.055 ( 0.08 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Reference treatment v ITT Population - Test treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.07
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.023
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.049
         upper limit
    		 0.002

    Secondary: Changes from baseline at each clinic visit in pre-dose R5 - R20/R5

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose R5 - R20/R5
    End point description
    R5 and R20 were measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.05 ( 0.21 )
    -0.081 ( 0.235 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.595
    Method
    		 Mixed models analysis
    Parameter type
    		 Median difference (net)
    Point estimate
    0.022
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.059
         upper limit
    		 0.103

    Secondary: Changes from baseline at each clinic visit in post-dose R5 - R20/R5

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    End point title
    		 Changes from baseline at each clinic visit in post-dose R5 - R20/R5
    End point description
    R5 and R20 were measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    -0.16 ( 0.2 )
    -0.162 ( 0.193 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.901
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.004
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.071
         upper limit
    		 0.063

    Secondary: Changes from baseline at each clinic visit in pre-dose distal capacitive reactance at 5 Hz (X5)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose distal capacitive reactance at 5 Hz (X5)
    End point description
    Distal capacitive reactance at 5 Hz was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    0.01 ( 0.13 )
    0.029 ( 0.099 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.416
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.016
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.053
         upper limit
    		 0.022

    Secondary: Changes from baseline at each clinic visit in post-dose distal capacitive reactance at 5 Hz (X5)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose distal capacitive reactance at 5 Hz (X5)
    End point description
    Distal capacitive reactance at 5 Hz was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: kPa/L/s
        arithmetic mean (standard deviation)
    0.047 ( 0.118 )
    0.046 ( 0.08 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.696
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.03

    Secondary: Changes from baseline at each clinic visit in pre-dose resonant frequency (Fres)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose resonant frequency (Fres)
    End point description
    Resonant frequency was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: Hz
        arithmetic mean (standard deviation)
    -1.62 ( 3.86 )
    -3.11 ( 5.19 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.116
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.275
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.32
         upper limit
    		 2.87

    Secondary: Changes from baseline at each clinic visit in post-dose resonant frequency (Fres)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose resonant frequency (Fres)
    End point description
    Resonant frequency was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: Hz
        arithmetic mean (standard deviation)
    -4.94 ( 4.6 )
    -4.85 ( 5.55 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.678
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.363
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.09
         upper limit
    		 1.365

    Secondary: Changes from baseline at each clinic visit in pre-dose area of reactance (AX)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose area of reactance (AX)
    End point description
    The area of reactance was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5.
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: Hz*kPa/L/s
        arithmetic mean (standard deviation)
    -0.119 ( 1.103 )
    -0.448 ( 1.224 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Reference treatment v ITT Population - Test treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.19
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.277
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.693

    Secondary: Changes from baseline at each clinic visit in post-dose area of reactance (AX)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose area of reactance (AX)
    End point description
    Area of reactance was measured by Impulse Oscillometry. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: Hz*kPa/L/s
        arithmetic mean (standard deviation)
    -0.694 ( 1.071 )
    -0.788 ( 1.067 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.891
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.265
         upper limit
    		 0.305

    Secondary: Changes from baseline at each clinic visit in pre-dose residual volume (RV)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose residual volume (RV)
    End point description
    Residual volume was measured by plethysmographic assessment. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    -0.04 ( 0.382 )
    -0.037 ( 0.452 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.693
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.036
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.217
         upper limit
    		 0.145

    Secondary: Changes from baseline at each clinic visit in post-dose residual volume (RV)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose residual volume (RV)
    End point description
    Residual volume was measured by plethysmographic assessment. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    -0.09 ( 0.443 )
    -0.007 ( 0.537 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.245
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.125
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.338
         upper limit
    		 0.088

    Secondary: Changes from baseline at each clinic visit in pre-dose inspiratory capacity/total lung capacity (IC/TLC)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose inspiratory capacity/total lung capacity (IC/TLC)
    End point description
    Inspiratory capacity/total lung capacity was measured by plethysmographic assessment. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: percentage
        arithmetic mean (standard deviation)
    -0.178 ( 6.562 )
    -0.417 ( 8.38 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.772
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.372
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.168
         upper limit
    		 2.912

    Secondary: Changes from baseline at each clinic visit in post-dose inspiratory capacity/total lung capacity (IC/TLC)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose inspiratory capacity/total lung capacity (IC/TLC)
    End point description
    Inspiratory capacity/total lung capacity was measured by plethysmographic assessment. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: percentage
        arithmetic mean (standard deviation)
    1.596 ( 7.03 )
    -1.389 ( 7.846 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.221
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.696
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.046
         upper limit
    		 4.438

    Secondary: Changes from baseline at each clinic visit in pre-dose functional residual capacity (FRC)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose functional residual capacity (FRC)
    End point description
    Functional residual capacity was measured by plethysmographic assessment. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    -0.079 ( 0.511 )
    0.101 ( 0.732 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.099
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.205
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.45
         upper limit
    		 0.04

    Secondary: Changes from baseline at each clinic visit in post-dose functional residual capacity (FRC)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose functional residual capacity (FRC)
    End point description
    Functional residual capacity was measured by plethysmographic assessment. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    -0.129 ( 0.486 )
    0.165 ( 0.762 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.051
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.252
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.505
         upper limit
    		 0.001

    Secondary: Changes from baseline at each clinic visit in pre-dose FEV1

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose FEV1
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    -0.059 ( 0.264 )
    0.051 ( 0.244 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.068
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.095
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.197
         upper limit
    		 0.007

    Secondary: Changes from baseline at each clinic visit in post-dose FEV1

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    End point title
    		 Changes from baseline at each clinic visit in post-dose FEV1
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    0.108 ( 0.242 )
    0.148 ( 0.279 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.557
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.031
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.134
         upper limit
    		 0.073

    Secondary: Changes from baseline at each clinic visit in pre-dose forced expiratory vital capacity/slow inspiratory vital capacity (FVC/ISVC)

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose forced expiratory vital capacity/slow inspiratory vital capacity (FVC/ISVC)
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: integer
        arithmetic mean (standard deviation)
    0.004 ( 0.075 )
    -0.036 ( 0.112 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Reference treatment v ITT Population - Test treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.184
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.021
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.01
         upper limit
    		 0.051

    Secondary: Changes from baseline at each clinic visit in post-dose forced expiratory vital capacity/slow inspiratory vital capacity (FVC/ISVC)

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    End point title
    		 Changes from baseline at each clinic visit in post-dose forced expiratory vital capacity/slow inspiratory vital capacity (FVC/ISVC)
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: integer
        arithmetic mean (standard deviation)
    0.026 ( 0.128 )
    -0.025 ( 0.102 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.092
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.036
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.006
         upper limit
    		 0.078

    Secondary: Changes from baseline at each clinic visit in pre-dose FEF25-75%

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose FEF25-75%
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    -0.025 ( 0.46 )
    0.127 ( 0.569 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.186
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.137
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.342
         upper limit
    		 0.068

    Secondary: Changes from baseline at each clinic visit in post-dose FEF25-75%

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    End point title
    		 Changes from baseline at each clinic visit in post-dose FEF25-75%
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    0.402 ( 0.567 )
    0.345 ( 0.752 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.609
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.069
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.198
         upper limit
    		 0.335

    Secondary: Changes from baseline at each clinic visit in pre-dose FEF50%

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    End point title
    		 Changes from baseline at each clinic visit in pre-dose FEF50%
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    -0.165 ( 0.598 )
    0.07 ( 0.647 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.069
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.478
         upper limit
    		 0.018

    Secondary: Changes from baseline at each clinic visit in post-dose FEF50%

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    End point title
    		 Changes from baseline at each clinic visit in post-dose FEF50%
    End point description
    Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: liters
        arithmetic mean (standard deviation)
    0.39 ( 0.671 )
    0.428 ( 0.765 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.97
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.006
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.296
         upper limit
    		 0.308

    Secondary: Severe asthma exacerbations

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    End point title
    		 Severe asthma exacerbations
    End point description
    Severe asthma exacerbations between date of Visit 2 and the end of the study are considered for the analysis.
    End point type
    Secondary
    End point timeframe
    At each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: integer
    1
    1
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Test treatment v ITT Population - Reference treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.949
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.059
         upper limit
    		 15.171

    Secondary: Change from baseline in average asthma symptom score

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    End point title
    		 Change from baseline in average asthma symptom score
    End point description
    Total asthma symptom score has been calculated as sum of total day-time asthma symptom score and total night-time asthma symptom score of a day. "Overall" data are reported here.
    End point type
    Secondary
    End point timeframe
    Daily from Visit 1 to Visit 5.
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: integer
        arithmetic mean (standard deviation)
    -0.438 ( 2.509 )
    -0.517 ( 1.567 )
    No statistical analyses for this end point

    Secondary: Change from baseline in percentage of asthma symptom-free days

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    End point title
    		 Change from baseline in percentage of asthma symptom-free days
    End point description
    An asthma symptom-free day is a day with total asthma symptom score = 0."Overall" data are reported here
    End point type
    Secondary
    End point timeframe
    Daily, at each clinic visit from Visit 1 to Visit 5.
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: days
        arithmetic mean (standard deviation)
    5.9 ( 31.5 )
    8.6 ( 35.2 )
    No statistical analyses for this end point

    Secondary: Changes from baseline in percentage of rescue medication-free days

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    End point title
    		 Changes from baseline in percentage of rescue medication-free days
    End point description
    A rescue medication-free day is a day with number of puffs of rescue medication = 0. "Overall" data are reported here
    End point type
    Secondary
    End point timeframe
    Daily, at each clinic visit from Visit 1 to Visit 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: days
        arithmetic mean (standard deviation)
    0.28 ( 10.5 )
    2.24 ( 9.88 )
    No statistical analyses for this end point

    Secondary: ACT scores

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    End point title
    		 ACT scores
    End point description
    The ACT survey is a patient-completed questionnaire with 5 items assessing asthma symptoms (daytime and nocturnal), use of rescue medications, and the effect of asthma on daily functioning. Only data from Visit 5 are reported here.
    End point type
    Secondary
    End point timeframe
    At visits 1, 2 and 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: digit
        arithmetic mean (standard deviation)
    22.8 ( 2 )
    23.1 ( 1.7 )
    Statistical analysis title
    		 Test treatment vs Reference treatment
    Comparison groups
    ITT Population - Reference treatment v ITT Population - Test treatment
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.694
    Method
    		 ANCOVA
    Parameter type
    		 adjusted mean difference
    Point estimate
    -0.137
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.827
         upper limit
    		 0.553

    Secondary: Changes from baseline in heart rate

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    End point title
    		 Changes from baseline in heart rate
    End point description
    Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were measured after 10 min rest in sitting position. From visit 2 to visit 5 the measurements were done before the administration of the morning dose of the study drug (pre-dose).
    End point type
    Secondary
    End point timeframe
    At Visit 1 and pre-dose at each clinic visit from Visit 2 to Visit 5
    End point values
    		 Safety population - Test treatment safety population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: beats/min
        arithmetic mean (standard deviation)
    -4 ( 9 )
    -1.2 ( 8.3 )
    No statistical analyses for this end point

    Secondary: Changes from baseline in systolic blood pressure

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    End point title
    		 Changes from baseline in systolic blood pressure
    End point description
    Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were measured after 10 min rest in sitting position. From visit 2 to visit 5 the measurements were done before the administration of the morning dose of the study drug (pre-dose).
    End point type
    Secondary
    End point timeframe
    At Visit 1 and pre-dose at each clinic visit from Visit 2 to Visit 5.
    End point values
    		 Safety population - Test treatment safety population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: mmHg
        arithmetic mean (standard deviation)
    -1.2 ( 12.9 )
    -1.8 ( 13.3 )
    No statistical analyses for this end point

    Secondary: Changes from baseline in diastolic blood pressure

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    End point title
    		 Changes from baseline in diastolic blood pressure
    End point description
    Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were measured after 10 min rest in sitting position. From visit 2 to visit 5 the measurements were done before the administration of the morning dose of the study drug (pre-dose).
    End point type
    Secondary
    End point timeframe
    At Visit 1 and pre-dose at each clinic visit from Visit 2 to Visit 5
    End point values
    		 Safety population - Test treatment safety population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: mmHg
        arithmetic mean (standard deviation)
    -0.4 ( 8.8 )
    -0.6 ( 8.8 )
    No statistical analyses for this end point

    Secondary: Change from baseline in average of rescue medication

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    End point title
    		 Change from baseline in average of rescue medication
    End point description
    Use of rescue medication (number of puffs/day) has been calculated as the sum of the number of puffs taken during the day and during the night. Only "Overall" data are reported here.
    End point type
    Secondary
    End point timeframe
    At Visits 3, 4, and 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: puffs/day
        arithmetic mean (standard deviation)
    -0.017 ( 0.223 )
    -0.054 ( 0.241 )
    No statistical analyses for this end point

    Secondary: Use of concomitant medications to treat asthma exacerbations

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    End point title
    		 Use of concomitant medications to treat asthma exacerbations
    End point description
    End point type
    Secondary
    End point timeframe
    At Visits 3, 4, and 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: number of subject
    2
    1
    No statistical analyses for this end point

    Secondary: Severe asthma exacerbations

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    End point title
    		 Severe asthma exacerbations
    End point description
    End point type
    Secondary
    End point timeframe
    At Visits 3, 4, and 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: number of subject
    1
    1
    No statistical analyses for this end point

    Secondary: Unscheduled hospitalizations

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    End point title
    		 Unscheduled hospitalizations
    End point description
    End point type
    Secondary
    End point timeframe
    At Visits 3, 4, and 5
    End point values
    		 ITT Population - Test treatment ITT Population - Reference treatment
    Number of subjects analysed
    54
    54
    Units: number of subject
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events/serious adverse events were measured at each visit, starting from Visit 0 to Visit 5 and to follow-up (phone contact)
    Adverse event reporting additional description
    Treatment-emergent adverse events (TEAEs) were reported in the two treatment groups in the safety population. Treatment-emergent adverse events (TEAEs) = adverse events which occurred after the first intake of the study medication
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Safety population - Test treatment
    Reporting group description
    		 Foster® NEXThaler® (beclomethasone dipropionate 100 μg plus formoterol 6 μg per actuation), 2 inhalations b.i.d. (daily dose of BDP 400 μg plus FF 24 μg) plus Seretide® Accuhaler® placebo, 1 inhalation b.i.d.

    Reporting group title
    Safety population - Reference treatment
    Reporting group description
    		 Seretide Accuhaler: fixed combination of fluticasone propionate 250 μg plus salmeterol xinafoate 50 μg per actuation

    Serious adverse events
    		 Safety population - Test treatment Safety population - Reference treatment
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Infections and infestations
    Bronchopneumonia
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (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: 1%
    Non-serious adverse events
    		 Safety population - Test treatment Safety population - Reference treatment
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 54 (25.93%)
    10 / 54 (18.52%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    3 / 54 (5.56%)
    0 / 54 (0.00%)
         occurrences all number
    4
    0
    Tachycardia
         subjects affected / exposed
    3 / 54 (5.56%)
    0 / 54 (0.00%)
         occurrences all number
    3
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    2 / 54 (3.70%)
    0 / 54 (0.00%)
         occurrences all number
    3
    0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Feeling cold
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    asthma
         subjects affected / exposed
    2 / 54 (3.70%)
    1 / 54 (1.85%)
         occurrences all number
    2
    1
    Cough
         subjects affected / exposed
    1 / 54 (1.85%)
    3 / 54 (5.56%)
         occurrences all number
    1
    3
    Dyspnoea
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1
    Wheezing
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Hyperprolactinaemia
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Gastrointestinal infection
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    1 / 54 (1.85%)
    2 / 54 (3.70%)
         occurrences all number
    1
    2
    Oral candidiasis
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    1 / 54 (1.85%)
    0 / 54 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 54 (0.00%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1

    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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