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    Clinical Trial Results:
    A Single-Dose, Open-Label, Randomized, 3-way Crossover, Clinical Pharmacology Study of CHF 1535 100/6 pMDI (fixed combination of Beclomethasone Dipropionate 100 μg plus Formoterol Fumarate 6 μg) with or without Spacer Device versus the free Combination of Licensed Beclomethasone pMDI and Formoterol pMDI in Asthmatic Adolescent Patients and One Open-Arm for Adult Patients as Control Group treated with CHF 1535 100/6 pMDI.

    Summary
    EudraCT number
    2011-005108-14
    Trial protocol
    PL  
    Global end of trial date
    24 Aug 2012

    Results information
    Results version number
    v1(current)
    This version publication date
    10 Nov 2017
    First version publication date
    10 Nov 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CCD-1104-PR-0062
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01803087
    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, Chiesi Farmaceutici S.p.A., Chiesi Farmaceutici S.p.A., +39 0521 2791, ClinicalTrials_info@chiesi.com
    Scientific contact
    Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., Chiesi Farmaceutici S.p.A., +39 0521 2791, 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
    22 Mar 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Aug 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Aug 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate, in adolescents, the systemic exposure to B17MP (active metabolite of BDP) as AUC0-t, after inhalation of CHF 1535 100/6 pMDI with and without spacer device (AeroChamber Plus™) in comparison with the already licensed free combination of BDP pMDI and Formoterol pMDI without spacer.
    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
    21 Feb 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
    Poland: 60
    Worldwide total number of subjects
    60
    EEA total number of subjects
    60
    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)
    30
    Adults (18-64 years)
    30
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects were recruited from subjects attending the outpatient’s hospital clinics or independent Clinical Research Organisation. Subjects were selected and randomised according to the inclusion criteria.

    Pre-assignment
    Screening details
    In total, 30 adolescents and 30 adults were screened. No subjects failed screening; all 30 adolescents were randomised to one of 3 treatment sequences (TEST 1/REF/TEST 2, TEST 2/TEST 1/REF, REF/TEST 2/TEST 1), i.e., 10 subjects per treatment sequence, and received study drugs, and all 30 adults received a single dose of control drug (CTR)

    Period 1
    Period 1 title
    Overall trial by sequence (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded
    Blinding implementation details
    As this is an open-label study, blinding is not applicable.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    TEST 1/REF/TEST 2
    Arm description
    Adolescent subjects took the following single-day treatments in sequence: • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.
    Arm type
    Experimental

    Investigational medicinal product name
    CHF 1535
    Investigational medicinal product code
    Other name
    beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    CHF 1535 100/6 pMDI, 4 puffs (total dose of BDP 400 μg / FF 24 μg) CHF 1535 100/6 pMDI, without (TEST 1) or with (TEST 2) AeroChamber Plus™

    Investigational medicinal product name
    beclomethasone dipropionate + formoterol fumarate
    Investigational medicinal product code
    Other name
    BDP, FF
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)

    Arm title
    TEST 2/TEST 1/REF
    Arm description
    Adolescent subjects took the following single-day treatments in sequence: • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.
    Arm type
    Experimental

    Investigational medicinal product name
    CHF 1535
    Investigational medicinal product code
    Other name
    beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    CHF 1535 100/6 pMDI, 4 puffs (total dose of BDP 400 μg / FF 24 μg) CHF 1535 100/6 pMDI, without (TEST 1) or with (TEST 2) AeroChamber Plus™

    Investigational medicinal product name
    beclomethasone dipropionate + formoterol fumarate
    Investigational medicinal product code
    Other name
    BDP, FF
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)

    Arm title
    REF/TEST 2/TEST 1
    Arm description
    Adolescent subjects took the following single-day treatments in sequence: • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.
    Arm type
    Experimental

    Investigational medicinal product name
    CHF 1535
    Investigational medicinal product code
    Other name
    beclomethasone dipropionate (BDP), formoterol fumarate (FF), Foster
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    CHF 1535 100/6 pMDI, 4 puffs (total dose of BDP 400 μg / FF 24 μg) CHF 1535 100/6 pMDI, without (TEST 1) or with (TEST 2) AeroChamber Plus™

    Investigational medicinal product name
    beclomethasone dipropionate + formoterol fumarate
    Investigational medicinal product code
    Other name
    BDP, FF
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Free combination of BDP pMDI plus FF pMDI, 4 + 4 puffs (total dose of BDP 400 μg + FF 24 μg)

    Arm title
    CONTROL
    Arm description
    Adult patients (N=30) receiving a single dose of control drug (CTR) = 4 puffs of fixed combination CHF 1535 100/6 pMDI, for a total dose of BDP 400 μg / FF 24 μg). Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.
    Arm type
    Active comparator

    Investigational medicinal product name
    Foster
    Investigational medicinal product code
    Other name
    CHF 1535 100/6 pMDI, beclomethasone / formoterol fixed combination
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    In one single-day treatment visit, subjects (all adults) were to take 4 puffs of fixed combination CHF 1535 100/6 pMDI (CONTROL treatment – CTR) for a total dose of BDP 400 μg / FF 24 μg.

    Number of subjects in period 1
    TEST 1/REF/TEST 2 TEST 2/TEST 1/REF REF/TEST 2/TEST 1 CONTROL
    Started
    10
    10
    10
    30
    Completed
    9
    10
    10
    30
    Not completed
    1
    0
    0
    0
         Protocol deviation
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    TEST 1/REF/TEST 2
    Reporting group description
    Adolescent subjects took the following single-day treatments in sequence: • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Reporting group title
    TEST 2/TEST 1/REF
    Reporting group description
    Adolescent subjects took the following single-day treatments in sequence: • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Reporting group title
    REF/TEST 2/TEST 1
    Reporting group description
    Adolescent subjects took the following single-day treatments in sequence: • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Reporting group title
    CONTROL
    Reporting group description
    Adult patients (N=30) receiving a single dose of control drug (CTR) = 4 puffs of fixed combination CHF 1535 100/6 pMDI, for a total dose of BDP 400 μg / FF 24 μg). Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Reporting group values
    TEST 1/REF/TEST 2 TEST 2/TEST 1/REF REF/TEST 2/TEST 1 CONTROL Total
    Number of subjects
    10 10 10 30 60
    Age categorical
    Units: Subjects
        Adolescents (12-17 years)
    10 10 10 0 30
        Adults (18-64 years)
    0 0 0 30 30
    Age continuous
    Units: years
        median (full range (min-max))
    16 (12 to 17) 14 (12 to 17) 16 (12 to 16) 40 (18 to 64) -
    Gender categorical
    Note: The sequence TEST 1/REF/ TEST 2 included one subject who discontinued the study due to a major protocol deviation.
    Units: Subjects
        Female
    6 5 5 14 30
        Male
    4 5 5 16 30

    End points

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    End points reporting groups
    Reporting group title
    TEST 1/REF/TEST 2
    Reporting group description
    Adolescent subjects took the following single-day treatments in sequence: • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Reporting group title
    TEST 2/TEST 1/REF
    Reporting group description
    Adolescent subjects took the following single-day treatments in sequence: • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Reporting group title
    REF/TEST 2/TEST 1
    Reporting group description
    Adolescent subjects took the following single-day treatments in sequence: • REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI for a total dose of BDP 400 μg + FF 24 μg. • TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using AeroChamber Plus™ for a total dose of BDP 400 μg / FF 24 μg); • TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI for a (total dose of BDP 400 μg / formoterol fumarate [FF] 24 μg); The 3 single-day treatment periods were separated by a wash-out period of minimum 7 and maximum 21 days. Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Reporting group title
    CONTROL
    Reporting group description
    Adult patients (N=30) receiving a single dose of control drug (CTR) = 4 puffs of fixed combination CHF 1535 100/6 pMDI, for a total dose of BDP 400 μg / FF 24 μg). Before the one-day single dose treatment period (Visit 2), the study included a two-days run-in period. A follow-up phone contact was performed within 7-10 days after treatment Visit 2.

    Subject analysis set title
    TEST 1 - PK/PD population
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.

    Subject analysis set title
    TEST 2 - PK/PD population
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.

    Subject analysis set title
    REF - PK/PD population
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.

    Subject analysis set title
    CTR - PK/PD population
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All subjects from the safety population excluding subjects without any valid PK/PD (i.e., potassium and glucose) measurement or with major protocol deviations significantly affecting PK/PD.

    Primary: B17MP Cmax

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    End point title
    B17MP Cmax
    End point description
    The value and time of the maximum drug concentration (Cmax and tmax) were indicators for the rate of absorption.
    End point type
    Primary
    End point timeframe
    At Visit 2, Visit 3 and Visit 4
    End point values
    TEST 1 - PK/PD population TEST 2 - PK/PD population REF - PK/PD population CTR - PK/PD population
    Number of subjects analysed
    28
    29
    29
    30
    Units: pg/mL
        arithmetic mean (standard deviation)
    1056 ± 1137
    1044 ± 439
    1116 ± 508
    1052 ± 465
    Statistical analysis title
    TEST 1 vs REF
    Comparison groups
    TEST 1 - PK/PD population v REF - PK/PD population
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [1]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    84.38
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    70.22
         upper limit
    101.38
    Notes
    [1] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects.
    Statistical analysis title
    TEST 2 vs REF
    Comparison groups
    TEST 2 - PK/PD population v REF - PK/PD population
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [2]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    97
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    80.92
         upper limit
    116.27
    Notes
    [2] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects.
    Statistical analysis title
    TEST 2 vs TEST 1
    Comparison groups
    TEST 1 - PK/PD population v TEST 2 - PK/PD population
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [3]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    114.96
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    95.67
         upper limit
    138.13
    Notes
    [3] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects
    Statistical analysis title
    TEST 1 vs CTR
    Comparison groups
    TEST 1 - PK/PD population v CTR - PK/PD population
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [4]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    90.83
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    72.46
         upper limit
    113.84
    Notes
    [4] - B17MP Cmax was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects

    Primary: B17MP AUC0-t

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    End point title
    B17MP AUC0-t
    End point description
    After single administration, the area under the plasma concentration versus time curve up to the last quantifiable concentration (AUC0-t) was used to measure the extent of absorption.
    End point type
    Primary
    End point timeframe
    At Visit 2, Visit 3 and Visit 4
    End point values
    TEST 1 - PK/PD population TEST 2 - PK/PD population REF - PK/PD population CTR - PK/PD population
    Number of subjects analysed
    28
    29
    29
    30
    Units: pg.h/mL
        arithmetic mean (standard deviation)
    2798 ± 846
    2724 ± 957
    3028 ± 965
    3107 ± 980
    Statistical analysis title
    TEST 1 vs REF
    Comparison groups
    TEST 1 - PK/PD population v REF - PK/PD population
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [5]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    91.69
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    81.64
         upper limit
    102.97
    Notes
    [5] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects.
    Statistical analysis title
    TEST 2 vs REF
    Comparison groups
    TEST 2 - PK/PD population v REF - PK/PD population
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [6]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    89.63
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    79.93
         upper limit
    100.5
    Notes
    [6] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects.
    Statistical analysis title
    TEST 2 vs TEST 1
    Comparison groups
    TEST 1 - PK/PD population v TEST 2 - PK/PD population
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [7]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    97.76
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    87.05
         upper limit
    109.78
    Notes
    [7] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects.
    Statistical analysis title
    TEST 1 vs CTR
    Comparison groups
    TEST 1 - PK/PD population v CTR - PK/PD population
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [8]
    Method
    Parameter type
    adjusted geometric means ratio
    Point estimate
    90.14
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    78.39
         upper limit
    103.65
    Notes
    [8] - B17MP AUC0-t was log-transformed and submitted to a linear model with treatment, sequence, period and subject within sequence as fixed effects.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    At each clinic visit from Visit 0 (pre-screening visit) to follow-up (phone call)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    TEST1
    Reporting group description
    TEST 1: 4 puffs of fixed combination CHF 1535 100/6 pMDI (total dose of BDP 400 μg / FF 24 μg);

    Reporting group title
    TEST2
    Reporting group description
    TEST 2: 4 puffs of fixed combination CHF 1535 100/6 pMDI using the AeroChamber Plus™ spacer device (total dose of BDP 400 μg / FF 24 μg);

    Reporting group title
    REF treatment
    Reporting group description
    REF: 4 + 4 puffs of free combination of BDP pMDI plus FF pMDI (total dose of BDP 400 μg + FF 24 μg);

    Reporting group title
    CTR Adults
    Reporting group description
    CTR: 4 puffs of a fixed combination CHF 1535 100/6 pMDI (total dose of BDP 400 μg / FF 24 μg).

    Serious adverse events
    TEST1 TEST2 REF treatment CTR Adults
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (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: 3.3%
    Non-serious adverse events
    TEST1 TEST2 REF treatment CTR Adults
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 29 (3.45%)
    3 / 29 (10.34%)
    4 / 30 (13.33%)
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    0
    1
    Tremor
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 30 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    0
    0
    2
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    0
    1
    0
    0

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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.
    There are no limitations nor caveats applicable to this summary of results.
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