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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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 MULTICENTER, MULTINATIONAL, SINGLE-DOSE, OPEN LABEL, RANDOMIZED, 2-WAY CROSSOVER, CLINICAL PHARMACOLOGY STUDY OF CHF 1535 100/6 NEXT DPI® (FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE 100 µg PLUS FORMOTEROL FUMARATE 6 µg) VERSUS THE FREE COMBINATION OF LICENSED BECLOMETHASONE DPI AND FORMOTEROL DPI IN ASTHMATIC ADOLESCENTS AND ADULTS PATIENTS

    Summary
    EudraCT number
    		 2010-018947-33
    Trial protocol
    		 GB   DK  
    Global end of trial date
    25 Sep 2011

    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

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CCD-1017-PR-0034
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01191424
    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 Clinical Trials, Chiesi Farmaceutici SpA, ClinicalTrials_info@chiesi.com
    Scientific contact
    Clinical Trial Transparency Manager, Chiesi Clinical Trials, Chiesi Farmaceutici SpA, ClinicalTrials_info@chiesi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000548-PIP01-09
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Sep 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    25 Sep 2011
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Sep 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the systemic exposure to beclomethasone-17-monopropionate (B17MP; active metabolite of beclomethasone dipropionate [BDP]) as area under the plasma drug concentration-time curve calculated to the last quantifiable time point (AUC0-t), after 4 single inhalations of the fixed combination CHF 1535 100/6 NEXT DPI® (total dose: BDP 400 μg/formoterol fumarate 24 μg) in comparison with a free combination of BDP dry powder inhaler (DPI) and formoterol DPI licensed products in the asthmatic adolescent and adult patient populations.
    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
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Oct 2010
    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
    United Kingdom: 30
    Country: Number of subjects enrolled
    Denmark: 28
    Worldwide total number of subjects
    58
    EEA total number of subjects
    58
    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)
    28
    Adults (18-64 years)
    30
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 33 adult patients from 1 study centre in the UK and 29 adolescents from 1 study centre in Denmark were screened in this 2-way cross over study. One adolescent and 3 adult patients failed screening: 28 adolescent and 30 adult patients were randomised.

    Period 1
    Period 1 title
    Overall trial by sequence (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    The treatment in this study was administered open-label, i.e., the investigator and patients knew the identity of the drug.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence T--R
    Arm description
    		 Test Treatment (fixed combination): CHF 1535 100/6 NEXT DPI® 4 inhalations (total daily dose at the clinic: BDP 400 μg/FF 24 μg), Reference Treatment (free combination): BDP 100 μg DPI 4 inhalations (Clenil® Pulvinal®, total daily dose at the clinic: 400 μg) + formoterol fumarate 12 μg DPI 2 inhalations (Foradil®Aerolizer®, total daily dose at the clinic: 24 μg).
    Arm type
    		 experimental - active comparator

    Investigational medicinal product name
    CHF 1535 NEXT DPI® - BDP DPI+FF DPI
    Investigational medicinal product code
    Other name
    beclomethasone dipropionate, formoterol fumarate
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    No specific treatment was provided during the run-in period. At the end of the run-in period, patients started the first 1-day treatment period (Visit 2) and were randomised to either TEST (CHF 1535 NEXT DPI® 100 + 6 μg) or REFERENCE (free combination of BDP DPI 100 μg plus formoterol DPI 12 μg) study treatment. Prior to the next visit, patients underwent a 1- to 3-week wash-out period, before the next study treatment administration at Visit 3. During the second 1-day treatment period (Visit 3), patients were assigned to the other study treatment according to the sequence specified in the randomisation list and the study cross-over design.

    Arm title
    		 Sequence R--T
    Arm description
    		 Reference Treatment (free combination): BDP 100 μg DPI 4 inhalations (Clenil® Pulvinal®, total daily dose at the clinic: 400 μg) + formoterol fumarate 12 μg DPI 2 inhalations (Foradil®Aerolizer®, total daily dose at the clinic: 24 μg). Test Treatment (fixed combination): CHF 1535 100/6 NEXT DPI® 4 inhalations (total daily dose at the clinic: BDP 400 μg/FF 24 μg)
    Arm type
    		 Active comparator - Experimental

    Investigational medicinal product name
    BDP+FF DPI - CHF1535 NEXT DPI
    Investigational medicinal product code
    Other name
    beclomethasone dipropionate, formoterol fumarate
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    No specific treatment was provided during the run-in period. At the end of the run-in period, patients started the first 1-day treatment period (Visit 2) and were randomised to either TEST (CHF 1535 NEXT DPI® 100 + 6 μg) or REFERENCE (free combination of BDP DPI 100 μg plus formoterol DPI 12 μg) study treatment. Prior to the next visit, patients underwent a 1- to 3-week wash-out period, before the next study treatment administration at Visit 3. During the second 1-day treatment period (Visit 3), patients were assigned to the other study treatment according to the sequence specified in the randomisation list and the study cross-over design.

    Number of subjects in period 1
    		Sequence T--R Sequence R--T
    Started
    29
    29
    wash out
    28
    29
    Completed
    28
    29
    Not completed
    1
    0
         Consent withdrawn by subject
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Sequence T--R
    Reporting group description
    		 Test Treatment (fixed combination): CHF 1535 100/6 NEXT DPI® 4 inhalations (total daily dose at the clinic: BDP 400 μg/FF 24 μg), Reference Treatment (free combination): BDP 100 μg DPI 4 inhalations (Clenil® Pulvinal®, total daily dose at the clinic: 400 μg) + formoterol fumarate 12 μg DPI 2 inhalations (Foradil®Aerolizer®, total daily dose at the clinic: 24 μg).

    Reporting group title
    Sequence R--T
    Reporting group description
    		 Reference Treatment (free combination): BDP 100 μg DPI 4 inhalations (Clenil® Pulvinal®, total daily dose at the clinic: 400 μg) + formoterol fumarate 12 μg DPI 2 inhalations (Foradil®Aerolizer®, total daily dose at the clinic: 24 μg). Test Treatment (fixed combination): CHF 1535 100/6 NEXT DPI® 4 inhalations (total daily dose at the clinic: BDP 400 μg/FF 24 μg)

    Reporting group values
    		 Sequence T--R Sequence R--T Total
    Number of subjects
    		 29 29 58
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 14 14 28
        Adults (18-64 years)
    		 15 15 30
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 0 ( 0 ) 0 ( 0 ) -
    Gender categorical
    Units: Subjects
        Female
    		 13 13 26
        Male
    		 16 16 32
    Subject analysis sets

    Subject analysis set title
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adult subjects who used at least one dose of study medication.

    Subject analysis set title
    CHF 1535NEXT DPI treatment phase - Adolescents - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adolescent subjects who used at least one dose of study medication.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adults - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adult subjects who used at least one dose of study medication.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adolescents - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adolescent subjects who used at least one dose of study medication.

    Subject analysis sets values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD CHF 1535 100/6 NEXT DPI treatment phase - Adults - Safety CHF 1535NEXT DPI treatment phase - Adolescents - Safety BDP DPI + FF DPI treatment phase - Adults - Safety BDP DPI + FF DPI treatment phase - Adolescents - Safety
    Number of subjects
    30
    27
    30
    27
    30
    28
    30
    27
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    27
    0
    27
    0
    28
    0
    27
        Adults (18-64 years)
    30
    0
    30
    0
    30
    0
    30
    0
        From 65-84 years
    0
    0
    0
    0
    0
    0
    0
    0
        85 years and over
    0
    0
    0
    0
    0
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    32.6 ( 10.8 )
    13.7 ( 1.7 )
    37.6 ( 9.7 )
    14.1 ( 1.7 )
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    13
    12
    13
    12
    13
    13
    13
    12
        Male
    17
    15
    17
    15
    17
    15
    17
    15

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Sequence T--R
    Reporting group description
    		 Test Treatment (fixed combination): CHF 1535 100/6 NEXT DPI® 4 inhalations (total daily dose at the clinic: BDP 400 μg/FF 24 μg), Reference Treatment (free combination): BDP 100 μg DPI 4 inhalations (Clenil® Pulvinal®, total daily dose at the clinic: 400 μg) + formoterol fumarate 12 μg DPI 2 inhalations (Foradil®Aerolizer®, total daily dose at the clinic: 24 μg).

    Reporting group title
    Sequence R--T
    Reporting group description
    		 Reference Treatment (free combination): BDP 100 μg DPI 4 inhalations (Clenil® Pulvinal®, total daily dose at the clinic: 400 μg) + formoterol fumarate 12 μg DPI 2 inhalations (Foradil®Aerolizer®, total daily dose at the clinic: 24 μg). Test Treatment (fixed combination): CHF 1535 100/6 NEXT DPI® 4 inhalations (total daily dose at the clinic: BDP 400 μg/FF 24 μg)

    Subject analysis set title
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For PK/PD population is intended the subpopulation of the safety population without any major protocol deviation that could affect the PK/PD.

    Subject analysis set title
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adult subjects who used at least one dose of study medication.

    Subject analysis set title
    CHF 1535NEXT DPI treatment phase - Adolescents - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adolescent subjects who used at least one dose of study medication.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adults - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adult subjects who used at least one dose of study medication.

    Subject analysis set title
    BDP DPI + FF DPI treatment phase - Adolescents - Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomised adolescent subjects who used at least one dose of study medication.

    Primary: Plasma AUC0-t for B17MP

    		 Close Top of page
    End point title
    		 Plasma AUC0-t for B17MP
    End point description
    For the purpose of the primary endpoint analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK. After single administration, the area under the plasma concentration versus time curve up to the last quantifiable concentration (AUC0-t) is used to measure the extent of absorption.
    End point type
    Primary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    2407.37 ( 562.9 )
    3396.37 ( 659.36 )
    2058.24 ( 523.38 )
    3115.96 ( 1452.69 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.17
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.101
         upper limit
    		 1.252
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.14
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.027
         upper limit
    		 1.276

    Secondary: Plasma BDP AUC0-t

    		 Close Top of page
    End point title
    		 Plasma BDP AUC0-t
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    531.57 ( 170.6 )
    874.83 ( 384.71 )
    424.36 ( 181.78 )
    744.42 ( 455.82 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.31
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.17
         upper limit
    		 1.48
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.28
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.05
         upper limit
    		 1.56

    Secondary: Plasma BDP AUC0-0.5h

    		 Close Top of page
    End point title
    		 Plasma BDP AUC0-0.5h
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    408.53 ( 118.48 )
    545.52 ( 191.73 )
    290.53 ( 123.94 )
    409.41 ( 232.19 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.49
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.33
         upper limit
    		 1.66
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.45
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.26
         upper limit
    		 1.67

    Secondary: Plasma BDP AUC0-inf

    		 Close Top of page
    End point title
    		 Plasma BDP AUC0-inf
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    597.4 ( 162.19 )
    827.18 ( 304.72 )
    503.6 ( 180.95 )
    807.75 ( 469.8 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.19
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.07
         upper limit
    		 1.32
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.08
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.25

    Secondary: Plasma BDP Cmax

    		 Close Top of page
    End point title
    		 Plasma BDP Cmax
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg/mL
        arithmetic mean (standard deviation)
    1546.3 ( 506.4 )
    2042.5 ( 877.7 )
    918.9 ( 396.4 )
    1243.6 ( 706.9 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.77
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.55
         upper limit
    		 2.02
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.75
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.51
         upper limit
    		 2.03

    Secondary: Plasma BDP tmax

    		 Close Top of page
    End point title
    		 Plasma BDP tmax
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hours
        median (full range (min-max))
    0.1 (0.1 to 0.3)
    0.1 (0.1 to 0.3)
    0.1 (0.1 to 0.3)
    0.1 (0.1 to 0.3)
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.063
    Method
    		 Wilcoxon signed rank test
    Confidence interval
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 > 0.999
    Method
    		 Wilcoxon signed rank test
    Confidence interval

    Secondary: Plasma BDP t1/2

    		 Close Top of page
    End point title
    		 Plasma BDP t1/2
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hours
        arithmetic mean (standard deviation)
    0.29 ( 0.07 )
    0.36 ( 0.11 )
    0.39 ( 0.15 )
    0.43 ( 0.16 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.74
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 0.83
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.82
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 0.95

    Secondary: Plasma formoterol AUC0-t

    		 Close Top of page
    End point title
    		 Plasma formoterol AUC0-t
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    93.44 ( 17.9 )
    115.05 ( 28.96 )
    67.8 ( 17.33 )
    78.9 ( 22.15 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.31
         upper limit
    		 1.49
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.46
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.36
         upper limit
    		 1.56

    Secondary: Plasma formoterol AUC0-0.5h

    		 Close Top of page
    End point title
    		 Plasma formoterol AUC0-0.5h
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    18.45 ( 4.11 )
    24.93 ( 7.48 )
    8 ( 2.6 )
    10.73 ( 3.74 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    2.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.17
         upper limit
    		 2.66
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    2.37
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.16
         upper limit
    		 2.6

    Secondary: Plasma formoterol AUC0-∞

    		 Close Top of page
    End point title
    		 Plasma formoterol AUC0-∞
    End point description
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*h/mL
        arithmetic mean (standard deviation)
    129.02 ( 24.73 )
    151.62 ( 43.96 )
    89.71 ( 24.46 )
    102.13 ( 34.58 )
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.45
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.34
         upper limit
    		 1.57
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.48
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.36
         upper limit
    		 1.62

    Secondary: Plasma formoterol Cmax

    		 Close Top of page
    End point title
    		 Plasma formoterol Cmax
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK.
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg/mL
        arithmetic mean (standard deviation)
    57.79 ( 16.888 )
    87.39 ( 31.69 )
    21.535 ( 6.835 )
    31.83 ( 12.42 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    2.71
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.45
         upper limit
    		 3
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    2.83
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.56
         upper limit
    		 3.13

    Secondary: Plasma formoterol Tmax

    		 Close Top of page
    End point title
    		 Plasma formoterol Tmax
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hr
        median (full range (min-max))
    0.1 (0.1 to 0.3)
    0.1 (0.1 to 0.3)
    0.25 (0.1 to 1)
    0.1 (0.1 to 1)
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0
    Method
    		 Wilcoxon signed rank test
    Confidence interval
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    BDP DPI + FF DPI treatment phase - Adolescents - PK/PD v CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.145
    Method
    		 wilcoxon signed rank test
    Confidence interval

    Secondary: Plasma formoterol T½

    		 Close Top of page
    End point title
    		 Plasma formoterol T½
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hr
        arithmetic mean (standard deviation)
    4.87 ( 1.69 )
    4.25 ( 0.84 )
    4.18 ( 1.87 )
    3.7 ( 0.91 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Statistical analysis description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.18
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.33
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.16
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.05
         upper limit
    		 1.28

    Secondary: Plasma B17MP AUC0-0.05h

    		 Close Top of page
    End point title
    		 Plasma B17MP AUC0-0.05h
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    185.02 ( 64.03 )
    356.61 ( 110.13 )
    126.26 ( 47 )
    245.68 ( 139.7 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.34
         upper limit
    		 1.68
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Statistical analysis description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.59
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.37
         upper limit
    		 1.84

    Secondary: Plasma B17MP AUC0-∞

    		 Close Top of page
    End point title
    		 Plasma B17MP AUC0-∞
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg*hr/mL
        arithmetic mean (standard deviation)
    3065.42 ( 826.52 )
    3937.07 ( 792.82 )
    2809.98 ( 773.24 )
    3710.1 ( 1605.52 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.09
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 1.17
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.11
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.25

    Secondary: Plasma B17MP Cmax

    		 Close Top of page
    End point title
    		 Plasma B17MP Cmax
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    End point type
    Secondary
    End point timeframe
    at Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: pg/mL
        arithmetic mean (standard deviation)
    612 ( 186.5 )
    1000.4 ( 246.5 )
    481.2 ( 113.7 )
    830.9 ( 355.5 )
    Statistical analysis title
    		 ChF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.26
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.16
         upper limit
    		 1.36
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.25
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 1.37

    Secondary: Plasma B17MP Tmax

    		 Close Top of page
    End point title
    		 Plasma B17MP Tmax
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hr
        median (full range (min-max))
    1 (0.3 to 2)
    0.5 (0.1 to 2)
    1 (0.3 to 2)
    1 (0.3 to 2)
    Statistical analysis title
    		 ChF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.008
    Method
    		 wilcoxon signed rank test
    Confidence interval
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.005
    Method
    		 wilcoxon signed rank test
    Confidence interval

    Secondary: Plasma B17MP t1/2

    		 Close Top of page
    End point title
    		 Plasma B17MP t1/2
    End point description
    For the purpose of the secondary endpoints analysis, the results are reported based on the PK population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PK
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hr
        arithmetic mean (standard deviation)
    3.45 ( 0.74 )
    2.94 ( 1.03 )
    3.88 ( 0.94 )
    3.02 ( 0.99 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 0.99
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.97
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.08

    Secondary: Plasma potassium Cmin

    		 Close Top of page
    End point title
    		 Plasma potassium Cmin
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: mEq/L
        arithmetic mean (standard deviation)
    3.717 ( 0.254 )
    3.795 ( 0.212 )
    3.72 ( 0.214 )
    3.902 ( 0.197 )
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Statistical analysis description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.998
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.977
         upper limit
    		 1.02
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Statistical analysis description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.971
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.948
         upper limit
    		 0.995

    Secondary: Plasma potassium Tmin

    		 Close Top of page
    End point title
    		 Plasma potassium Tmin
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    at Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hours
        median (full range (min-max))
    4 (0 to 6)
    1.88 (0.5 to 7.8)
    4 (0 to 8)
    4 (1 to 7.8)
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.162
    Method
    		 wilcoxon signed rank test
    Confidence interval
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    BDP DPI + FF DPI treatment phase - Adolescents - PK/PD v CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.008
    Method
    		 wilcoxon signed rank test
    Confidence interval

    Secondary: Plasma potassium AUC0-t

    		 Close Top of page
    End point title
    		 Plasma potassium AUC0-t
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: mEq*h/L
        arithmetic mean (standard deviation)
    31.81 ( 1.94 )
    31.68 ( 1.45 )
    32.14 ( 1.79 )
    32.35 ( 1.32 )
    Statistical analysis title
    		 ChF1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.01
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1

    Secondary: Plasma glucose Cmax

    		 Close Top of page
    End point title
    		 Plasma glucose Cmax
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: mg/dL
        arithmetic mean (standard deviation)
    128.6 ( 22.9 )
    160.1 ( 35.3 )
    126.3 ( 17.1 )
    148.4 ( 14.5 )
    Statistical analysis title
    		 CHf1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.07
    Statistical analysis title
    		 CHf1535 NEXT DPI vs BDP DPI + FF DPI in adolescen
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.15

    Secondary: Plasma glucose Tmax

    		 Close Top of page
    End point title
    		 Plasma glucose Tmax
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hours
        median (full range (min-max))
    4.02 (4 to 6.1)
    4 (3.9 to 8)
    4.02 (4 to 8)
    4 (3.9 to 6)
    Statistical analysis title
    		 Chf1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.487
    Method
    		 wilcoxon signed rank test
    Confidence interval
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.216
    Method
    		 wilcoxon signed rank test
    Confidence interval

    Secondary: Plasma glucose AUC0-2h

    		 Close Top of page
    End point title
    		 Plasma glucose AUC0-2h
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: mg*hr/dL
        arithmetic mean (standard deviation)
    180.99 ( 11.55 )
    187.83 ( 16.9 )
    178.5 ( 10.78 )
    183.95 ( 12.81 )
    Statistical analysis title
    		 Chf1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1.03
    Statistical analysis title
    		 CHf1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.05

    Secondary: Plasma glucose AUC0-t

    		 Close Top of page
    End point title
    		 Plasma glucose AUC0-t
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: mg*hr/dL
        arithmetic mean (standard deviation)
    848.52 ( 84.71 )
    956.7 ( 128.81 )
    829.42 ( 61.48 )
    910.22 ( 72.76 )
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.05
    Statistical analysis title
    		 CHf1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 1.1

    Secondary: Plasma cortisol Cmin

    		 Close Top of page
    End point title
    		 Plasma cortisol Cmin
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    at Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: ng/mL
        arithmetic mean (standard deviation)
    38.98 ( 28.87 )
    15.01 ( 13.93 )
    40.98 ( 31.09 )
    13.58 ( 8.06 )
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.16
    Statistical analysis title
    		 CHf1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.2

    Secondary: Plasma cortisol Tmin

    		 Close Top of page
    End point title
    		 Plasma cortisol Tmin
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: hours
        median (full range (min-max))
    4.02 (2 to 8.2)
    6 (2 to 8)
    4.02 (2 to 8.1)
    4.03 (2 to 7.9)
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.695
    Method
    		 Wilcoxon signed rank testc
    Confidence interval
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.768
    Method
    		 Wilcoxon signed rank testc
    Confidence interval

    Secondary: Plasma cortisol AUC0-t

    		 Close Top of page
    End point title
    		 Plasma cortisol AUC0-t
    End point description
    For the purpose of the secondary pharmacodynamic endpoints analysis, the results are reported based on the PD population, namely the subpopulation of the safety population without any major protocol deviation that could affect the PD
    End point type
    Secondary
    End point timeframe
    At Visit 2 and Visit 3
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: ng*hr/mL
        arithmetic mean (standard deviation)
    571.93 ( 377.99 )
    257.09 ( 148.51 )
    596.53 ( 356.59 )
    264.86 ( 112.11 )
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.07
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.06

    Secondary: Peak FEV1

    		 Close Top of page
    End point title
    		 Peak FEV1
    End point description
    Pulmonary function values are calculated on the base of the safety population
    End point type
    Secondary
    End point timeframe
    At Visits 2 and 3. Lung Function (FEV1, FVC) was evaluated during each treatment period (Visit 2 and 3) at the scheduled time pre- and post-drug administration.
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: Liters
        arithmetic mean (standard deviation)
    3.799 ( 0.928 )
    3.049 ( 0.676 )
    3.819 ( 0.908 )
    3.15 ( 0.71 )
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 least square mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.052
         upper limit
    		 0.013
    Statistical analysis title
    		 CHf1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 least square mean difference
    Point estimate
    -0.099
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.227
         upper limit
    		 0.029

    Secondary: FEV1 AUC0-8h/8h

    		 Close Top of page
    End point title
    		 FEV1 AUC0-8h/8h
    End point description
    Pulmonary function values are calculated on the base of the safety population
    End point type
    Secondary
    End point timeframe
    At Visits 2 and 3. Lung Function (FEV1, FVC) was evaluated during each treatment period (Visit 2 and 3) at the scheduled time pre- and post-drug administration.
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: Liters
        arithmetic mean (standard deviation)
    3.687 ( 0.904 )
    2.906 ( 0.64 )
    3.712 ( 0.904 )
    2.932 ( 0.644 )
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.993
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.984
         upper limit
    		 1.001
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    0.993
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.964
         upper limit
    		 1.023

    Secondary: Time average heart rate AUC0-8h/8h

    		 Close Top of page
    End point title
    		 Time average heart rate AUC0-8h/8h
    End point description
    Time average heart rate (AUC0-8h/8h) values are calculated on the base of the safety population
    End point type
    Secondary
    End point timeframe
    At Visits 2 and 3. Heart rate was evaluated during each treatment period at the scheduled pre- ad post- drug administration
    End point values
    		 CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD BDP DPI + FF DPI treatment phase - Adults - PK/PD BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects analysed
    30
    27
    30
    27
    Units: bpm
        arithmetic mean (standard deviation)
    74 ( 9 )
    80.77 ( 8.72 )
    73 ( 9 )
    77.19 ( 9.61 )
    Statistical analysis title
    		 CHF 1535 NEXT DPI vs BDP DPI + FF DPI in adults
    Comparison groups
    CHF 1535 100/6 NEXT DPI treatment phase - Adults - PK/PD v BDP DPI + FF DPI treatment phase - Adults - PK/PD
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.03
    Statistical analysis title
    		 CHF1535 NEXT DPI vs BDP DPI + FF DPI in adolescent
    Comparison groups
    CHF 1535NEXT DPI treatment phase - Adolescents - PK/PD v BDP DPI + FF DPI treatment phase - Adolescents - PK/PD
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    		 ANOVA
    Parameter type
    		 ratio of geometric means
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.01
         upper limit
    		 1.09

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    For the overall duration of the study
    Adverse event reporting additional description
    All analyses were performed on the Safety Population. The number and percentage of patients experiencing AEs, study treatment-related AEs, SAEs and treatment-emergent AEs (TEAEs) leading to study discontinuation and severe AEs was presented for each treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.1
    Reporting groups
    Reporting group title
    CHF1535 NEXT DPI - Adults - Safety
    Reporting group description
    		 -

    Reporting group title
    CHF1535 NEXT DPI - Adolescents - Safety
    Reporting group description
    		 -

    Reporting group title
    BDP DPI + FF DPI - Adults - Safety
    Reporting group description
    		 -

    Reporting group title
    BDP DPI + FF DPI - Adolescents - Safety
    Reporting group description
    		 -

    Serious adverse events
    		 CHF1535 NEXT DPI - Adults - Safety CHF1535 NEXT DPI - Adolescents - Safety BDP DPI + FF DPI - Adults - Safety BDP DPI + FF DPI - Adolescents - Safety
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 27 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 CHF1535 NEXT DPI - Adults - Safety CHF1535 NEXT DPI - Adolescents - Safety BDP DPI + FF DPI - Adults - Safety BDP DPI + FF DPI - Adolescents - Safety
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 30 (40.00%)
    1 / 28 (3.57%)
    9 / 30 (30.00%)
    2 / 27 (7.41%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 30 (23.33%)
    0 / 28 (0.00%)
    5 / 30 (16.67%)
    0 / 27 (0.00%)
         occurrences all number
    7
    0
    5
    0
    Tremor
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 27 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 28 (3.57%)
    0 / 30 (0.00%)
    0 / 27 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrointestinal disorders
    Mouth ulceration
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 27 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 28 (0.00%)
    2 / 30 (6.67%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Oral herpes
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 28 (0.00%)
    1 / 30 (3.33%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Tonsillitis
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 28 (0.00%)
    0 / 30 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    0
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Jul 2010
    The total volume of blood that was withdrawn for the entire study was increased from 75 mL (adolescents) to 145 mL for patients in the adult population with the following changes to the volume of blood collected for the following PK and PD parameters for the adult population: - Formoterol: 9 blood samples of 3 mL. - BDP/B17MP: 9 blood samples of 2 mL. - Potassium: 9 blood samples of 1 mL. - Glucose: 9 blood samples of 1.2 mL. - Cortisol: 9 blood samples of 1 mL.

    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.
    No limitations and caveats are reported in the study document.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 23:40:29 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA