Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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


    The EU Clinical Trials Register currently displays   38596   clinical trials with a EudraCT protocol, of which   6341   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An open-label, crossover, interventional Phase IV study to compare the ease of use of tobramycin inhalation powder with tobramycin inhalation solution and nebulized colistimethate for the treatment of pulmonary Pseudomonas aeruginosa in patients with cystic fibrosis Due to EudraCT system limitations, which EMA is aware of, results of crossover studies and data using 999 as data points are not accurately represented in this record. Please go to https://www.novctrd.com/CtrdWeb/home.nov for complete trial results

    Summary
    EudraCT number
    2012-001565-33
    Trial protocol
    GB   DE   ES   IE  
    Global end of trial date
    20 Oct 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    06 Jul 2018
    First version publication date
    06 Jul 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    CTBM100C2403
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01844778
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    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
    20 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Oct 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare as a primary indicator for ease of use the mean cumulative time required to set up the delivery device (including preparation of the treatment), administer the drug, and clean the delivery device for TIP administered with the T-326 Inhaler, with the mean cumulative time to perform the same activities (including disinfection of the device, where applicable) for the patient’s usual (pre-study prescribed) inhaled antibiotic treatment for P. aeruginosa.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. Rescue medication for pulmonary exacerbations was allowed in this study.If a patient experienced a pulmonary exacerbation and/or worsening of the disease condition, he/she was to be treated as deemed appropriate by the investigator.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Aug 2013
    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
    Spain: 6
    Country: Number of subjects enrolled
    Switzerland: 8
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    Germany: 19
    Country: Number of subjects enrolled
    Ireland: 2
    Worldwide total number of subjects
    60
    EEA total number of subjects
    52
    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)
    1
    Adolescents (12-17 years)
    3
    Adults (18-64 years)
    56
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Each participant was assigned to 1 of 3 treatment arms, TIS/TIP, COLI/TIP, or TIP/TIP with the first treatment cycle based on the participant's usual antibiotic treatment. Then all participants were crossed-over to receive TIP for the second cycle of treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    TIS/TIP
    Arm description
    During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tobramycin inhalation solution (TIS)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment

    Arm title
    COLI/TIP
    Arm description
    During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant\'s usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
    Arm type
    Active comparator

    Investigational medicinal product name
    Colistimethate (COLI)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose andregimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off treatment (cycling regimen), depending on local treatment guidelines

    Arm title
    TIP/TIP
    Arm description
    During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tobramycin inhaltion powder
    Investigational medicinal product code
    TBM100
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

    Number of subjects in period 1
    TIS/TIP COLI/TIP TIP/TIP
    Started
    14
    28
    18
    Safety Set 1 (at least 1 dose, cycle 1)
    14
    28
    18
    Safety Set 2 (at least 1 dose, cycle 2)
    12
    25
    15
    Completed
    12
    25
    14
    Not completed
    2
    3
    4
         Adverse event, non-fatal
    -
    2
    2
         Consent withdrawn by subject
    2
    -
    -
         Protocol deviation
    -
    1
    2

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    TIS/TIP
    Reporting group description
    During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

    Reporting group title
    COLI/TIP
    Reporting group description
    During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant\'s usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

    Reporting group title
    TIP/TIP
    Reporting group description
    During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

    Reporting group values
    TIS/TIP COLI/TIP TIP/TIP Total
    Number of subjects
    14 28 18 60
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 1 1
        Adolescents (12-17 years)
    1 1 1 3
        Adults (18-64 years)
    13 27 16 56
        From 65-84 years
    0 0 0 0
        85 years and over
    0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    27.4 ± 6.82 28.4 ± 9.86 26.6 ± 7.25 -
    Gender, Male/Female
    Units: Participants
        Female
    4 10 7 21
        Male
    10 18 11 39

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    TIS/TIP
    Reporting group description
    During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

    Reporting group title
    COLI/TIP
    Reporting group description
    During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant\'s usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

    Reporting group title
    TIP/TIP
    Reporting group description
    During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

    Primary: Mean total administration time

    Close Top of page
    End point title
    Mean total administration time [1]
    End point description
    The mean total time for administration of TIP via T-326 inhaler versus the total time for administration of COLI or TIS was assessed from information entered by participants into an ediary during the last 7 days prior to the last dose of a cycle. The total time included the setup, preparation, administration and cleaning/disinfection time.
    End point type
    Primary
    End point timeframe
    days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not done on the primary outcome measure.
    End point values
    TIS/TIP COLI/TIP TIP/TIP
    Number of subjects analysed
    14
    28
    18
    Units: minutes
    arithmetic mean (standard deviation)
        Cycle 1 (n=8,17,14)
    37 ± 22.06
    16.4 ± 9.54
    4.2 ± 2.02
        Cycle 2 (n=10,16,11)
    5 ± 2.04
    3.8 ± 1.7
    3.4 ± 2.06
    No statistical analyses for this end point

    Secondary: Change in P. aeruginosa sputum density

    Close Top of page
    End point title
    Change in P. aeruginosa sputum density
    End point description
    Sputum samples were sent to a central laboratory at the start and end of 2 treatment periods. The absolute change in the number of colony forming units (CFU) of Pseudomonas aeruginosa in sputum = the value of end of on/off treatment period of the cycle minus the pre-dose value at the start of that cycle. A negative change from baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)
    End point values
    TIS/TIP COLI/TIP TIP/TIP
    Number of subjects analysed
    14
    28
    18
    Units: log10 CFU/mL
    arithmetic mean (standard deviation)
        Cycle 1, on-treatment change (n=11,22,9)
    -1.4 ± 1.85
    -0.6 ± 1.88
    -1.7 ± 2.87
        Cycle 1, off-treatment change (n=10,20,8)
    0.2 ± 1.98
    -0.6 ± 2.36
    -0.2 ± 1.56
        Cycle 2, on-treatment (n=9,16,5)
    -0.9 ± 1.66
    -0.5 ± 1.65
    -1.6 ± 1.53
        Cycle 2, off-treatment (n=9,18,5)
    0 ± 0.95
    0.5 ± 2.55
    0 ± 0.91
    No statistical analyses for this end point

    Secondary: Number of participants with any contaminated delivery device

    Close Top of page
    End point title
    Number of participants with any contaminated delivery device
    End point description
    Devices used to administer the drugs (the T-326 inhaler and nebulisers) were swabbed for contamination testing at the start and end of each treatment cycle (or discontinuation visit if the participant withdrew). No assessments were required from the T-326 inhaler when participants started the treatment period (days 1 and 57). Microbial contamination was measured according to device type and the frequency of organism growth (light/ moderate/ heavy). All nebulisers (neb) used by the participants were analyzed, including those for inhaling other medications, like mucolytics.
    End point type
    Secondary
    End point timeframe
    days (d) 1, 28, 57, 84
    End point values
    TIS/TIP COLI/TIP TIP/TIP
    Number of subjects analysed
    14
    28
    18
    Units: Participants
        P. a biotype 2 - dry,d1,neb, moderate,(n=0,0,1)
    9999
    9999
    1
        A. baumannii,d1,neb,heavy,n=0,7,0
    9999
    1
    9999
        A. junii,d1,neb,moderate,n=0,7,0
    9999
    1
    9999
        A.lwoffi,d1,neb,light,n=0,7,0
    9999
    2
    9999
        H. parainfluenza,d1,neb,light,n=0,7,0
    9999
    1
    9999
        O. anthropic,d1,neb,heavy,n=0,7,0
    9999
    1
    9999
        P. fluorescens,d1,neb,light,n=0,7,0
    9999
    1
    9999
        P. putida,d1,neb,light,n=0,7,0
    9999
    1
    9999
        P. stutzeri,d1,neb,moderate,n=0,7,0
    9999
    1
    9999
        S.liquefaciens,d1,neb,light,n=0,7,0
    9999
    1
    9999
        S. multivorum,d1,neb,light,n=0,7,0
    9999
    1
    9999
        S. maltophilia,d1,neb,light,n=0,7,0
    9999
    1
    9999
        Acinetobacter species,d28,neb,light,n=0,6,0
    9999
    1
    9999
        C. indologenes,d28,neb,moderate,n=0,6,0
    9999
    1
    9999
        D. acidovorans,d 28,neb,light,n=0,6,0
    9999
    1
    9999
        P. fluorescens,d28,neb,light,n=0,6,0
    9999
    2
    9999
        S. paucimobilis,d28,neb,heavy,n=0,6,0
    9999
    1
    9999
        S. aureus,d28,neb,light,n=0,6,0
    9999
    1
    9999
        P. a biotype 2 - dry,d57,neb,light,n=1,0,0
    1
    9999
    9999
        S. aureus,d84,T-326,light,n=1,0,0
    1
    9999
    9999
    No statistical analyses for this end point

    Secondary: Minimum inhibitory concentration (MIC) - MIC50 and MIC90 tobramycin values

    Close Top of page
    End point title
    Minimum inhibitory concentration (MIC) - MIC50 and MIC90 tobramycin values
    End point description
    MIC50/90 is the lowest concentration required to inhibit 50%/90% of the isolates tested. The MIC50/90 of a range of antibiotics for P.aeruginosa was determined at the start and end of each treatment cycle, and at the end of the off-treatment period of the second cycle.
    End point type
    Secondary
    End point timeframe
    days 1, 28, 57, 84, 112
    End point values
    TIS/TIP COLI/TIP TIP/TIP
    Number of subjects analysed
    14
    28
    18
    Units: ug/mL
        MIC50: Day 1, n=14,27,18; m=27,51,29
    2
    2
    2
        MIC50: Day 28, n=13,23,13; m=25,46,21
    2
    2
    2
        MIC50: Day 57, n=11,19,15; m=23,34,24
    4
    4
    2
        MIC50: Day 84, n=12,17,11; m=25,29,18
    4
    4
    2
        MIC50: Day 112, n=12,19,12; m=24,33,19
    2
    2
    1
        MIC90: Day 1, n=14,27,18; m=27,51,29
    256
    16
    64
        MIC90: Day 28, n=13,23,13; m=25,46,21
    256
    16
    64
        MIC90: Day 57, n=11,19,15; m=23,34,24
    64
    16
    64
        MIC90: Day 84, n=12,17,11; m=25,29,18
    512
    32
    64
        MIC90: Day 112, n=12,19,12; m=24,33,19
    32
    32
    32
    No statistical analyses for this end point

    Secondary: Number of participants with post-inhalation bronchospasm

    Close Top of page
    End point title
    Number of participants with post-inhalation bronchospasm
    End point description
    Bronchospasm was defined as the relative decrease of 20% or more in forced expiratory volume in 1 second (FEV1) percent predicted from pre-dose to 15 to 45 minutes post-dose.
    End point type
    Secondary
    End point timeframe
    days 1, 28, 57, 84
    End point values
    TIS/TIP COLI/TIP TIP/TIP
    Number of subjects analysed
    14
    28
    18
    Units: Participants
        Day 1, n=8,17,14
    0
    1
    0
        Day 28, n=6,19,14
    0
    1
    0
        Day 57, n=10,22,13
    0
    0
    1
        Day 84, n=8,14,10
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
    Adverse event reporting additional description
    AE additional description
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Cycle 1 TIS/TIP
    Reporting group description
    Cycle 1 TIS/TIP

    Reporting group title
    Cycle 1 COLI/TIP
    Reporting group description
    Cycle 1 COLI/TIP

    Reporting group title
    Cycle 2 COLI/TIP
    Reporting group description
    Cycle 2 COLI/TIP

    Reporting group title
    Cycle 2 TIS/TIP
    Reporting group description
    Cycle 2 TIS/TIP

    Reporting group title
    Cycle 2 TIP/TIP
    Reporting group description
    Cycle 2 TIP/TIP

    Reporting group title
    Cycle 1 TIP/TIP
    Reporting group description
    Cycle 1 TIP/TIP

    Serious adverse events
    Cycle 1 TIS/TIP Cycle 1 COLI/TIP Cycle 2 COLI/TIP Cycle 2 TIS/TIP Cycle 2 TIP/TIP Cycle 1 TIP/TIP
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 14 (21.43%)
    9 / 28 (32.14%)
    3 / 25 (12.00%)
    3 / 12 (25.00%)
    2 / 15 (13.33%)
    3 / 18 (16.67%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Investigations
    Acoustic stimulation tests abnormal
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forced expiratory volume decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary function test decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sputum increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Faecaloma
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary tract disorder
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Fungal infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    3 / 14 (21.43%)
    6 / 28 (21.43%)
    3 / 25 (12.00%)
    3 / 12 (25.00%)
    0 / 15 (0.00%)
    2 / 18 (11.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
    0 / 4
    0 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    1 / 12 (8.33%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cycle 1 TIS/TIP Cycle 1 COLI/TIP Cycle 2 COLI/TIP Cycle 2 TIS/TIP Cycle 2 TIP/TIP Cycle 1 TIP/TIP
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 14 (35.71%)
    12 / 28 (42.86%)
    7 / 25 (28.00%)
    6 / 12 (50.00%)
    10 / 15 (66.67%)
    10 / 18 (55.56%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Forced expiratory volume decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Glucose urine present
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    1 / 12 (8.33%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 28 (7.14%)
    0 / 25 (0.00%)
    1 / 12 (8.33%)
    2 / 15 (13.33%)
    2 / 18 (11.11%)
         occurrences all number
    2
    2
    0
    2
    2
    2
    Epistaxis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Haemoptysis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    2 / 25 (8.00%)
    1 / 12 (8.33%)
    0 / 15 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    2
    1
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Rales
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Prolonged expiration
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Respiratory arrest
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Respiratory tract congestion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Sputum increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    2 / 15 (13.33%)
    3 / 18 (16.67%)
         occurrences all number
    1
    0
    0
    0
    2
    3
    Wheezing
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    1 / 12 (8.33%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Aphonia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    3 / 15 (20.00%)
    3 / 18 (16.67%)
         occurrences all number
    1
    0
    0
    0
    4
    10
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    1 / 12 (8.33%)
    0 / 15 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 25 (0.00%)
    1 / 12 (8.33%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    0
    Skin and subcutaneous tissue disorders
    Night sweats
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    1 / 12 (8.33%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    2 / 14 (14.29%)
    5 / 28 (17.86%)
    6 / 25 (24.00%)
    1 / 12 (8.33%)
    1 / 15 (6.67%)
    0 / 18 (0.00%)
         occurrences all number
    2
    5
    6
    1
    1
    0
    Cystitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 28 (10.71%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    3 / 15 (20.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    3
    0
    0
    3
    2
    Tongue fungal infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    1 / 15 (6.67%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 25 (4.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 25 (0.00%)
    0 / 12 (0.00%)
    0 / 15 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    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
    22 May 2014
    Threshold values for BUN (from ≥5.7 μmol/L to ≥14.28 mmol/L [≥40 mg/dL]) and serum creatinine (≥89 μmol/L to ≥176.8 μmol/L [≥2 mg/dL]) exclusion criteria were corrected for consistency with the Summary of Product Characteristics (SmPC)/ PI and to avoid unnecessary screening failures. The threshold value for serum creatinine in the treatment discontinuation criteria was corrected. The threshold value for BUN in the discontinuation criteria was deleted as not considered medically relevant. Creatinine clearance as an exclusion criterion was deleted due to the threshold value being updated to cover the detection of potential renal AEs. Audiology testing requirements at baseline and/or at the subsequent visits were updated to be in line with the SmPC and PI. They were at the discretion of the investigator. Audiology assessments were not required from a subset of patients at selected sites, but from all patients who had a medical history of hearing loss or who experience AEs related to hearing loss during the study. The wording for the primary objective was updated to clarify that the cumulative times required to a) set up the delivery device (including preparation of the treatment), b) administer the drug and c) clean the device (including disinfecting the nebulizers where applicable) are being compared between the T-326 Inhaler and the nebulizers. The wordings for the study purpose and for one secondary objective were updated to clarify that the testing of the inhalation devices for microbiological contamination relates to all nebulizers used by the patients, including those for inhaling other medications (e.g. mucolytics). Clarified that semi-quantitative culture data for non-P. aeruginosa pathogens was collected and analyzed for this study. Clarified that re-screening of patients was allowed.

    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.
    Due to EudraCT system limitations, which EMA is aware of, results of crossover studies and data using 999 as data points are not accurately represented in this record. Please go to https://www.novctrd.com/CtrdWeb/home.nov for complete trial results
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA