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   43857   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 Double Blind, Double Dummy, Randomized, Two Way Cross-Over Study To Compare The Effects Of Z7200 And Symbicort® Turbohaler On Functional Respiratory Imaging Parameters In Asthmatic Patients

    Summary
    EudraCT number
    		 2014-002151-26
    Trial protocol
    		 BE  
    Global end of trial date
    28 Nov 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Mar 2016
    First version publication date
    23 Mar 2016
    Other versions
    Summary report(s)
    		 Study Results Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    Z7200K02
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02227394
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 CRO protocol code number: FLUI-2014-125
    Sponsors
    Sponsor organisation name
    Zambon SpA
    Sponsor organisation address
    via Lillo Del Duca 10, Bresso, Italy, 20091
    Public contact
    Clinical Development, R&D Open Innovation Zambon SpA, +39 02.665241, clinicaltrials@zambongroup.com
    Scientific contact
    Clinical Development, R&D Open Innovation Zambon SpA, +39 02.665241, clinicaltrials@zambongroup.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Nov 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate the effect of the products under investigation on Functional Respiratory Imaging (FRI) parameters and evaluate the particle deposition with Computational Fluid Dynamics (CFD) in comparison to a reference product.
    Protection of trial subjects
    Salbutamol MDI was supplied as rescue medication at screening/enrolment visit and could have been used until 6 hours before the first study procedure. The use of concomitant inhalation drugs was maintained constant throughout the study. Patients who were on combination therapy were switched to ICS on the evening before the dosing days (Visits 2 and 3).
    Background therapy
    		 -
    Evidence for comparator
    		 The comparator is a product available on the market in EU (Symbicort Turbohaler, DPI) with the same active ingredients but at a different dose level.
    Actual start date of recruitment
    25 Aug 2014
    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
    Belgium: 20
    Worldwide total number of subjects
    20
    EEA total number of subjects
    20
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    13
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects are recruited at the clinic

    Pre-assignment
    Screening details
    		 Only patients who met all inclusion criteria and none of the exclusion criteria were enrolled in the study and entered the run-in period of 7 (minimum) to 31 (maximum) days . Bronchodilator therapy was washed out before dosing.

    Period 1
    Period 1 title
    Treatment period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    A double dummy technique was implemented. Patients were to receive a single dose consisting of 2 inhalations of either the test product or the reference product, according to the assigned treatment sequence, in the presence of the Investigator or authorized site personnel. In addition, patients were to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.

    Arms
    Arm title
    		 Treatment period
    Arm description
    		 -
    Arm type
    		 Cross-over experimental

    Investigational medicinal product name
    Z7200
    Investigational medicinal product code
    Other name
    Formoterol/budesonide combination product
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations by using dedicated RS-01 device

    Investigational medicinal product name
    Symbicort
    Investigational medicinal product code
    Other name
    Formoterol/budesonide combination product
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations by using multidose Turbohaler (Dry Powder Inhaler)

    Number of subjects in period 1
    		Treatment period
    Started
    20
    Completed
    20

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Treatment period
    Reporting group description
    		 -

    Reporting group values
    		 Treatment period Total
    Number of subjects
    		 20 20
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 0 0
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
        from 18 to 80 years
    		 20 20
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.5 ( 11.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 8 8
        Male
    		 12 12
    FEV1% predicted
    Units: Percentage
        arithmetic mean (standard deviation)
    		 96.79 ( 22.82 ) -
    Subject analysis sets

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all randomized patients who received at least one dose of study drug

    Subject analysis set title
    pre dose Z7200
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Z7200 administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Subject analysis set title
    pre- dose SYMBICORT
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Symbicort administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Subject analysis set title
    post- dose Z7200
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Z7200 administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Subject analysis set title
    Post-dose Symbicort
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Symbicort administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Subject analysis sets values
    		 Safety population pre dose Z7200 pre- dose SYMBICORT post- dose Z7200 Post-dose Symbicort
    Number of subjects
    20
    20
    20
    20
    20
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
        from 18 to 80 years
    20
    20
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    58.5 ( 11.6 )
    58.5 ( 11.6 )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    8
    8
        Male
    12
    12
    FEV1% predicted
    Units: Percentage
        arithmetic mean (standard deviation)
    96.79 ( 22.82 )
    96.79 ( 22.82 )
    ( )
    ( )
    ( )

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Treatment period
    Reporting group description
    		 -

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all randomized patients who received at least one dose of study drug

    Subject analysis set title
    pre dose Z7200
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Z7200 administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Subject analysis set title
    pre- dose SYMBICORT
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Symbicort administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Subject analysis set title
    post- dose Z7200
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Z7200 administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Subject analysis set title
    Post-dose Symbicort
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    all randomized patients who had correct Symbicort administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect

    Primary: Imaged Based Total Airway Volume (iVaw)

    		 Close Top of page
    End point title
    		 Imaged Based Total Airway Volume (iVaw)
    End point description
    End point type
    Primary
    End point timeframe
    Pre and post-dose
    End point values
    		 pre dose Z7200 pre- dose SYMBICORT post- dose Z7200 Post-dose Symbicort
    Number of subjects analysed
    20
    20
    20
    20
    Units: millilitre(s)
        arithmetic mean (standard deviation)
    49.03 ( 13.23 )
    48.58 ( 13.43 )
    51.1 ( 12.74 )
    50.83 ( 13.48 )
    Statistical analysis title
    		 iVaw post-dose differences
    Statistical analysis description
    change in pre and post dose value are compared in the statistical analysis (difference test vs reference)
    Comparison groups
    Post-dose Symbicort v post- dose Z7200
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.59
    Method
    		 t-test, 2-sided
    Confidence interval

    Primary: Imaged Based Total Airway Resistance (iRaw)

    		 Close Top of page
    End point title
    		 Imaged Based Total Airway Resistance (iRaw)
    End point description
    End point type
    Primary
    End point timeframe
    pre and post-dose
    End point values
    		 pre dose Z7200 pre- dose SYMBICORT post- dose Z7200 Post-dose Symbicort
    Number of subjects analysed
    20
    20
    20
    20
    Units: kPa/L
        arithmetic mean (standard deviation)
    0.034 ( 0.016 )
    0.037 ( 0.022 )
    0.025 ( 0.011 )
    0.026 ( 0.009 )
    Statistical analysis title
    		 iRaw post-dose differences
    Statistical analysis description
    change from pre-dose test vs reference difference
    Comparison groups
    post- dose Z7200 v Post-dose Symbicort
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.75
    Method
    		 t-test, 2-sided
    Confidence interval

    Primary: Lung dose of Budesonide

    		 Close Top of page
    End point title
    		 Lung dose of Budesonide
    End point description
    dosimetry simulation per inhalation of test vs reference (1 puff)
    End point type
    Primary
    End point timeframe
    post-dose
    End point values
    		 post- dose Z7200 Post-dose Symbicort
    Number of subjects analysed
    16
    16
    Units: microgram(s)/dose
        arithmetic mean (standard deviation)
    45.05 ( 6.66 )
    36.35 ( 12.94 )
    Statistical analysis title
    		 Dosimetry comparison budesonide
    Comparison groups
    post- dose Z7200 v Post-dose Symbicort
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.018
    Method
    		 t-test, 2-sided
    Confidence interval

    Primary: Lung dose of formoterol

    		 Close Top of page
    End point title
    		 Lung dose of formoterol
    End point description
    Dosimetry simulation of test vs reference per inhalation (1 puff)
    End point type
    Primary
    End point timeframe
    post-dose
    End point values
    		 post- dose Z7200 Post-dose Symbicort
    Number of subjects analysed
    16
    16
    Units: microgram(s)/dose
        arithmetic mean (standard deviation)
    1.26 ( 0.18 )
    0.88 ( 0.34 )
    Statistical analysis title
    		 Dosimetry comparison formoterol
    Comparison groups
    Post-dose Symbicort v post- dose Z7200
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 < 0.001
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: VAS dyspnea (pre 6MWT)

    		 Close Top of page
    End point title
    		 VAS dyspnea (pre 6MWT)
    End point description
    The VAS dyspnea was completed using an analogue scale from “very much worse” to “very much improved”. Rating was measured using a ruler in cm from the indication “unchanged”
    End point type
    Secondary
    End point timeframe
    before the exercise test (6 minutes walking test)
    End point values
    		 post- dose Z7200 Post-dose Symbicort
    Number of subjects analysed
    20
    20
    Units: percentage
    19
    8
    Statistical analysis title
    		 VAS dyspnea pre 6MWT difference
    Statistical analysis description
    VAS dyspnea measured after inhalation of test and reference before exercise test
    Comparison groups
    post- dose Z7200 v Post-dose Symbicort
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.034
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: VAS dyspnea (post 6MWT)

    		 Close Top of page
    End point title
    		 VAS dyspnea (post 6MWT)
    End point description
    The VAS dyspnea was completed using an analogue scale from “very much worse” to “very much improved” . Rating was measured using a ruler in cm from the indication “unchanged”
    End point type
    Secondary
    End point timeframe
    post exercise test (6MWT)
    End point values
    		 post- dose Z7200 Post-dose Symbicort
    Number of subjects analysed
    20
    20
    Units: percentage
    21
    16
    Statistical analysis title
    		 VAS dyspnea post 6MWT difference
    Comparison groups
    Post-dose Symbicort v post- dose Z7200
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.43
    Method
    		 t-test, 2-sided
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All AEs were collected and reported from signature of informed consent form up to Visit 4. Adverse events that occurred before the first dosing with study drugs were defined as pre-treatment AEs.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    safety population
    Reporting group description
    		 all subjects randomized with at least one dose of test or reference administered.

    Serious adverse events
    		 safety population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 safety population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 20 (10.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    1 / 20 (5.00%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Tue Apr 23 16:38:30 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA