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   43865   clinical trials with a EudraCT protocol, of which   7286   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 multicentre, multinational, open-label, randomised, parallel group clinical trial of Tobrineb®/Actitob®/ Bramitob® (Tobramycin solution for nebulisation, 300 mg twice daily in 4 ml unit dose vials) compared to Tobi® in the treatment of patients with cystic fibrosis and chronic infection with Pseudomonas Aeruginosa.

    Summary
    EudraCT number
    		 2006-006215-68
    Trial protocol
    		 CZ   HU   ES   DE   FR  
    Global end of trial date
    24 May 2010

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Jul 2017
    First version publication date
    09 Jul 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CMA-0631-PR-0010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00885365
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Chiesi Farmaceutici S.p.A.
    Sponsor organisation address
    Via Palermo, 26/A, Parma, Italy, 43126
    Public contact
    Clinical Trial Transparency, , Chiesi Farmaceutici S.p.A., 0521 2791, ClinicalTrials_info@chiesi.com
    Scientific contact
    Clinical Trial Transparency, , Chiesi Farmaceutici S.p.A., 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-000184-PIP02-14
    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
    24 May 2010
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 May 2010
    Global end of trial reached?
    Yes
    Global end of trial date
    24 May 2010
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate that CHF 1538 is non-inferior to TOBI in the primary efficacy variable forced expiratory volume in one second (FEV1) percent predicted in patients with cystic fibrosis (CF) and chronic infection of the lungs with Pseudomonas aeruginosa (P. aeruginosa) at the end of the treatment phase.
    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
    27 Apr 2009
    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
    Russian Federation: 69
    Country: Number of subjects enrolled
    Ukraine: 80
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Poland: 131
    Country: Number of subjects enrolled
    Czech Republic: 8
    Country: Number of subjects enrolled
    France: 10
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Hungary: 17
    Worldwide total number of subjects
    324
    EEA total number of subjects
    175
    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)
    84
    Adolescents (12-17 years)
    131
    Adults (18-64 years)
    109
    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 406 patients were screened for the study of whom 82 (20.2%) failed screening and 324 patients were randomized; 159 to the CHF 1538 group and 165 to the TOBI group.

    Pre-assignment period milestones
    Number of subjects started
    		 406 [1]
    Number of subjects completed
    		 324

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Failure to meet Inclusion/Exclusion criteria: 80
    Reason: Number of subjects
    		 Patient withdrew consent: 2
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: There were 82 screen failures.
    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Blind conditions could not be applied to this study due to the different volumes of the tobramycin solutions to be tested (CHF 1538 4 mL and TOBI 5 mL).

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 CHF 1538
    Arm description
    		 Tobramycin 300 mg/4 mL inhalation solution for nebulization, administered 300mg twice a day for 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bramitob
    Investigational medicinal product code
    Other name
    Tobrineb, Actitob, tobramycin
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    300mg administered twice a day for 4 weeks via the Pari LC Plus nebulizer

    Arm title
    		 TOBI
    Arm description
    		 Tobramycin 300 mg/5 mL inhalation solution for nebulization, administered 300mg twice a day for 4 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    TOBI
    Investigational medicinal product code
    Other name
    tobramycin
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    300mg administered twice a day for 4 weeks via Pari LC Plus Nebulizer

    Number of subjects in period 1
    		CHF 1538 TOBI
    Started
    159
    165
    Week 4 - End of "ON" Treatment
    155
    159
    Week 8 - End of "OFF" Treatment
    155
    159
    Completed
    155
    159
    Not completed
    4
    6
         Consent withdrawn by subject
    1
    -
         Adverse event, non-fatal
    2
    4
         Protocol deviation
    1
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    CHF 1538
    Reporting group description
    		 Tobramycin 300 mg/4 mL inhalation solution for nebulization, administered 300mg twice a day for 4 weeks

    Reporting group title
    TOBI
    Reporting group description
    		 Tobramycin 300 mg/5 mL inhalation solution for nebulization, administered 300mg twice a day for 4 weeks.

    Reporting group values
    		 CHF 1538 TOBI Total
    Number of subjects
    		 159 165 324
    Age categorical
    Age in years calculated as integer ((date of Screening - date of birth/365.25))
    Units: Subjects
        Children (6-12 years)
    		 47 56 103
        Adolescents (13-17 years)
    		 54 58 112
        Adults (> 17 years)
    		 58 51 109
    Gender categorical
    Units: Subjects
        Male
    		 72 85 157
        Female
    		 87 80 167
    Subject analysis sets

    Subject analysis set title
    CHF 1538 - ITT Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who took at least one dose of study medication (Bramitob), with available baseline FEV1 value and with at least one available post-baseline FEV1 value during treatment period.

    Subject analysis set title
    TOBI - ITT Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who took at least one dose of study medication (TOBI), with available baseline FEV1 value and with at least one available post-baseline FEV1 value during treatment period.

    Subject analysis set title
    CHF1538 - Safety Population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized patients who took at least one dose of study medication - Bramitob.

    Subject analysis set title
    TOBI - Safety Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who took at least one dose of study medication - TOBI.

    Subject analysis sets values
    		 CHF 1538 - ITT Population TOBI - ITT Population CHF1538 - Safety Population TOBI - Safety Population
    Number of subjects
    158
    163
    156
    168
    Age categorical
    Age in years calculated as integer ((date of Screening - date of birth/365.25))
    Units: Subjects
        Children (6-12 years)
    47
    56
    49
    54
        Adolescents (13-17 years)
    54
    57
    50
    62
        Adults (> 17 years)
    57
    50
    57
    52
    Age continuous
    Units:
        
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Male
    72
    84
    72
    85
        Female
    86
    79
    84
    83

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    CHF 1538
    Reporting group description
    		 Tobramycin 300 mg/4 mL inhalation solution for nebulization, administered 300mg twice a day for 4 weeks

    Reporting group title
    TOBI
    Reporting group description
    		 Tobramycin 300 mg/5 mL inhalation solution for nebulization, administered 300mg twice a day for 4 weeks.

    Subject analysis set title
    CHF 1538 - ITT Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who took at least one dose of study medication (Bramitob), with available baseline FEV1 value and with at least one available post-baseline FEV1 value during treatment period.

    Subject analysis set title
    TOBI - ITT Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who took at least one dose of study medication (TOBI), with available baseline FEV1 value and with at least one available post-baseline FEV1 value during treatment period.

    Subject analysis set title
    CHF1538 - Safety Population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized patients who took at least one dose of study medication - Bramitob.

    Subject analysis set title
    TOBI - Safety Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients who took at least one dose of study medication - TOBI.

    Primary: Change from Baseline to End of the Treatment Period of FEV1, expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change from Baseline to End of the Treatment Period of FEV1, expressed as Percentage of Predicted Normal
    End point description
    Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded in the CRF. Values reported in the system are "last observation carried forward" (LOCF).
    End point type
    Primary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    163
    Units: percentage predicted FEV1
    arithmetic mean (standard deviation)
        Week 4
    6.99 ( 9.52 )
    7.51 ( 9.63 )
    Statistical analysis title
    		 CHF 1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF).
    Comparison groups
    CHF 1538 - ITT Population v TOBI - ITT Population
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.64 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Means Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.58
         upper limit
    		 1.59
    Notes
    [1] - Non-inferiority was evaluated for the primary efficacy variable (change from baseline in FEV1 % predicted normal at Visit 4) by calculating the two-sided 95% CI for the difference in the LSMEANS between CHF 1538 and TOBI, from an analysis of covariance (ANCOVA) model including treatment and country as effects and baseline value as covariate.
    [2] - the p value reported here refers to the "treatment" as effect/factor

    Secondary: Change From Baseline to End of Week 2 of FEV1, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 of FEV1, Expressed as Percentage of Predicted Normal
    End point description
    Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded in the CRF.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 2 (Visit 3)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    163
    Units: percent
        arithmetic mean (standard deviation)
    6.7 ( 9.99 )
    6.93 ( 9.4 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 8 of FEV1, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 of FEV1, Expressed as Percentage of Predicted Normal
    End point description
    Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded in the CRF.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    155 [3]
    159 [4]
    Units: percent
        arithmetic mean (standard deviation)
    5.47 ( 11.88 )
    5.37 ( 11.11 )
    Notes
    [3] - this is the actual number of the patients analyzed
    [4] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 2 of FEV1, Expressed as liters

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 of FEV1, Expressed as liters
    End point description
    Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded in the CRF.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 2 (Visit 3)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    163
    Units: LIters
        arithmetic mean (standard deviation)
    0.18 ( 0.27 )
    0.19 ( 0.27 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 4 of FEV1, Expressed as liters

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 4 of FEV1, Expressed as liters
    End point description
    Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded in the CRF.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4). For Visit 4, LOCF values are reported.
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    155 [5]
    161 [6]
    Units: Liters
        arithmetic mean (standard deviation)
    0.2 ( 0.29 )
    0.21 ( 0.29 )
    Notes
    [5] - this is the actual number of the patients analyzed
    [6] - this is the actual number of the patients analyzed
    Statistical analysis title
    		 CHF1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF) values.
    Comparison groups
    CHF 1538 - ITT Population v TOBI - ITT Population
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    P-value
    		 = 0.634 [8]
    Method
    		 ANCOVA
    Parameter type
    		 least Square Means Difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.08
         upper limit
    		 0.05
    Notes
    [7] - Comparisons between treatment groups were made at Visit 4 by using the same ANCOVA model as for the primary variable. This model included the effects of treatment group and country as factors and baseline value as covariate.
    [8] - the p value reported here refers to the "treatment" as factor

    Secondary: Change From Baseline to End of Week 8 of FEV1, Expressed as liters

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 of FEV1, Expressed as liters
    End point description
    Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded in the CRF.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    155 [9]
    159 [10]
    Units: Liters
        arithmetic mean (standard deviation)
    0.16 ( 0.33 )
    0.16 ( 0.32 )
    Notes
    [9] - this is the actual number of the patients analyzed
    [10] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 2 of FVC, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 of FVC, Expressed as Percentage of Predicted Normal
    End point description
    FVC was measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 2 (Visit 3)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    156 [11]
    163
    Units: percent
        arithmetic mean (standard deviation)
    4.36 ( 10.81 )
    5.36 ( 10.03 )
    Notes
    [11] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 4 of FVC, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 4 of FVC, Expressed as Percentage of Predicted Normal
    End point description
    FVC was measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4). For Visit 4, LOCF values are reported.
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    156 [12]
    163
    Units: Percent
        arithmetic mean (standard deviation)
    4.8 ( 9.96 )
    5.48 ( 10.83 )
    Notes
    [12] - this is the actual number of the patients analyzed
    Statistical analysis title
    		 CHF1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF) values.
    Comparison groups
    TOBI - ITT Population v CHF 1538 - ITT Population
    Number of subjects included in analysis
    319
    Analysis specification
    Pre-specified
    Analysis type
    		 other [13]
    P-value
    		 = 0.63 [14]
    Method
    		 ANCOVA
    Parameter type
    		 least Square Means Difference
    Point estimate
    -0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.78
         upper limit
    		 1.69
    Notes
    [13] - Comparisons between treatment groups were made at Visit 4 by using the same ANCOVA model as for the primary variable. This model included the effects of treatment group and country as factors and baseline value as covariate.
    [14] - the p value reported here refers to the "treatment" as factor.

    Secondary: Change From Baseline to End of Week 8 of FVC, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 of FVC, Expressed as Percentage of Predicted Normal
    End point description
    FVC was measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5).
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    153 [15]
    159 [16]
    Units: percent
        arithmetic mean (standard deviation)
    2.7 ( 12.3 )
    5.04 ( 12.21 )
    Notes
    [15] - this is the actual number of the patients analyzed
    [16] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 2 of FVC, Expressed as liters

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 of FVC, Expressed as liters
    End point description
    FVC was measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 2 (Visit 3)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    156 [17]
    163
    Units: LIters
        arithmetic mean (standard deviation)
    0.14 ( 0.34 )
    0.16 ( 0.32 )
    Notes
    [17] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 4 of FVC, Expressed as liters

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 4 of FVC, Expressed as liters
    End point description
    FVC was measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4). For Visit 4, LOCF values are reported.
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    156 [18]
    163
    Units: Liters
        arithmetic mean (standard deviation)
    0.16 ( 0.34 )
    0.17 ( 0.36 )
    Notes
    [18] - this is the actual number of the patients analyzed
    Statistical analysis title
    		 CHF1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF) values.
    Comparison groups
    CHF 1538 - ITT Population v TOBI - ITT Population
    Number of subjects included in analysis
    319
    Analysis specification
    Pre-specified
    Analysis type
    		 other [19]
    P-value
    		 = 0.693 [20]
    Method
    		 ANCOVA
    Parameter type
    		 least Square Means Difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.06
    Notes
    [19] - Comparisons between treatment groups were made at Visit 4 by using the same ANCOVA model as for the primary variable. This model included the effects of treatment group and country as factors and baseline value as covariate.
    [20] - the p value reported here refers to the "treatment" as effect/factor

    Secondary: Change From Baseline to End of Week 8 of FVC, Expressed as liters

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 of FVC, Expressed as liters
    End point description
    FVC was measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    at Week 2 (Visit 3) and Week 8 (Visit 5)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    153 [21]
    159 [22]
    Units: Liters
        arithmetic mean (standard deviation)
    0.1 ( 0.38 )
    0.16 ( 0.39 )
    Notes
    [21] - this is the actual number of the patients analyzed
    [22] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 2 of FEF25-75%, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 of FEF25-75%, Expressed as Percentage of Predicted Normal
    End point description
    Difference in FEF25-75% was measured from baseline to weeks 2 (Visit 3), 4 (Visit 4), and 8 (Visit 5). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 2 (Visit 3)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    156 [23]
    162 [24]
    Units: Percent
        arithmetic mean (standard deviation)
    10.3 ( 17.07 )
    8.57 ( 19 )
    Notes
    [23] - this is the actual number of the patients analyzed
    [24] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 4 of FEF25-75%, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 4 of FEF25-75%, Expressed as Percentage of Predicted Normal
    End point description
    Difference in FEF25-75% was measured from baseline to weeks 2 (Visit 3), 4 (Visit 4), and 8 (Visit 5). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4). For Visit 4, LOCF values are reported.
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    157 [25]
    162 [26]
    Units: Percent
        arithmetic mean (standard deviation)
    10.22 ( 15.11 )
    9.25 ( 17.85 )
    Notes
    [25] - this is the actual number of the patients analyzed
    [26] - this is the actual number of the patients analyzed
    Statistical analysis title
    		 CHF1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF) values.
    Comparison groups
    CHF 1538 - ITT Population v TOBI - ITT Population
    Number of subjects included in analysis
    319
    Analysis specification
    Pre-specified
    Analysis type
    		 other [27]
    P-value
    		 = 0.777 [28]
    Method
    		 ANCOVA
    Parameter type
    		 least Square Means Difference
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.06
         upper limit
    		 4.09
    Notes
    [27] - Comparisons between treatment groups were made at Visit 4 by using the same ANCOVA model as for the primary variable. This model included the effects of treatment group and country as factors and baseline value as covariate.
    [28] - the p value reported here refers to the "treatment" as effect/factor

    Secondary: Change From Baseline to End of Week 8 of FEF25-75%, Expressed as Percentage of Predicted Normal

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 of FEF25-75%, Expressed as Percentage of Predicted Normal
    End point description
    Difference in FEF25-75% was measured from baseline to weeks 2 (Visit 3), 4 (Visit 4), and 8 (Visit 5). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    154 [29]
    158 [30]
    Units: Percent
        arithmetic mean (standard deviation)
    9.05 ( 19.59 )
    6.41 ( 20.46 )
    Notes
    [29] - this is the actual number of the patients analyzed
    [30] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 2 of FEF25-75%, Expressed as liters/sec

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 of FEF25-75%, Expressed as liters/sec
    End point description
    Difference in FEF25-75% was measured from baseline to weeks 2 (Visit 3), 4 (Visit 4), and 8 (Visit 5). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 2 (Visit 3)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    156 [31]
    162 [32]
    Units: Liters/sec
        arithmetic mean (standard deviation)
    0.32 ( 0.5 )
    0.28 ( 0.56 )
    Notes
    [31] - this is the actual number of the patients analyzed
    [32] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 4 of FEF25-75%, Expressed as liters/sec

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 4 of FEF25-75%, Expressed as liters/sec
    End point description
    Difference in FEF25-75% was measured from baseline to weeks 2 (Visit 3), 4 (Visit 4), and 8 (Visit 5). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4). For Visit 4, LOCF values are reported.
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    157 [33]
    162 [34]
    Units: Liters/sec
        arithmetic mean (standard deviation)
    0.33 ( 0.48 )
    0.29 ( 0.56 )
    Notes
    [33] - this is the actual number of the patients analyzed
    [34] - this is the actual number of the patients analyzed
    Statistical analysis title
    		 CHF1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF) values.
    Comparison groups
    CHF 1538 - ITT Population v TOBI - ITT Population
    Number of subjects included in analysis
    319
    Analysis specification
    Pre-specified
    Analysis type
    		 other [35]
    P-value
    		 = 0.505 [36]
    Method
    		 ANCOVA
    Parameter type
    		 least Square Means Difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.08
         upper limit
    		 0.15
    Notes
    [35] - Comparisons between treatment groups were made at Visit 4 by using the same ANCOVA model as for the primary variable. This model included the effects of treatment group and country as factors and baseline value as covariate.
    [36] - the p value reported here refers to the "treatment" as effect/factor

    Secondary: Change From Baseline to End of Week 8 of FEF25-75%, Expressed as liters/sec

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 of FEF25-75%, Expressed as liters/sec
    End point description
    Difference in FEF25-75% was measured from baseline to weeks 2 (Visit 3), 4 (Visit 4), and 8 (Visit 5). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    154 [37]
    158 [38]
    Units: liters/sec
        arithmetic mean (standard deviation)
    0.28 ( 0.57 )
    0.21 ( 0.67 )
    Notes
    [37] - this is the actual number of the patients analyzed
    [38] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change from baseline to End of Week 4 in Pseudomonas Log10 bacterial load in sputum

    		 Close Top of page
    End point title
    		 Change from baseline to End of Week 4 in Pseudomonas Log10 bacterial load in sputum
    End point description
    If a participant had more than one Pseudomonas aeruginosa (PA) morphotype at a given visit, and therefore more than one bacterial load value, then the bacterial load value corresponding to the highest tobramycin minimal inhibitory concentration (MIC) value regardless of the PA morphotype was used. If the tobramycin MIC value was the same for different PA morphotypes, then the bacterial load value corresponding to morphotype 1 (mucoid colony) was used. If morphotype 1 was not available, bacterial load value corresponding to morphotype 2 (dry colony) was used.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4).
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    152 [39]
    156 [40]
    Units: CFU/gram
        arithmetic mean (standard deviation)
    -2.14 ( 2.41 )
    -2.07 ( 2.2 )
    Notes
    [39] - this is the actual number of the patients analyzed
    [40] - this is the actual number of the patients analyzed
    Statistical analysis title
    		 CHF 1538 vs TOBI
    Comparison groups
    TOBI - ITT Population v CHF 1538 - ITT Population
    Number of subjects included in analysis
    308
    Analysis specification
    Pre-specified
    Analysis type
    		 other [41]
    P-value
    		 = 0.82 [42]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Means Difference
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.31
         upper limit
    		 0.39
    Notes
    [41] - Comparisons between treatment groups were made at Visit 4 by using the same ANCOVA model as for the primary variable. This model included the effects of treatment group and country as factors and baseline value as covariate
    [42] - the p value reported here refers to the "treatment" as effect/factor

    Secondary: Change from baseline to End of Week 8 in Pseudomonas Log10 bacterial load in sputum

    		 Close Top of page
    End point title
    		 Change from baseline to End of Week 8 in Pseudomonas Log10 bacterial load in sputum
    End point description
    If a participant had more than one Pseudomonas aeruginosa (PA) morphotype at a given visit, and therefore more than one bacterial load value, then the bacterial load value corresponding to the highest tobramycin minimal inhibitory concentration (MIC) value regardless of the PA morphotype was used. If the tobramycin MIC value was the same for different PA morphotypes, then the bacterial load value corresponding to morphotype 1 (mucoid colony) was used. If morphotype 1 was not available, bacterial load value corresponding to morphotype 2 (dry colony) was used.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5)
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    147 [43]
    147 [44]
    Units: CFU/gram
        arithmetic mean (standard deviation)
    -0.72 ( 2.17 )
    -0.87 ( 2.23 )
    Notes
    [43] - this is the actual number of the patients analyzed
    [44] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Tobramicyn MIC50 of Pseudomonas aeruginosa at week 4

    		 Close Top of page
    End point title
    		 Tobramicyn MIC50 of Pseudomonas aeruginosa at week 4
    End point description
    MIC50 values were calculated for three different Pseudomonas aeruginosa (PA) strains: - Morphotype 1: mucoid - Morphotype 2: dry - Morphotype 3: variant Overall MIC50 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal, then the MIC value for the isolate with the highest bacterial load value was used.
    End point type
    Secondary
    End point timeframe
    Week 4 (Visit 4).
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    126 [45]
    134 [46]
    Units: micrograms/mL
        number (not applicable)
    1
    0.5
    Notes
    [45] - this is the actual number of the patients analyzed
    [46] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Tobramicyn MIC50 of Pseudomonas aeruginosa at week 8

    		 Close Top of page
    End point title
    		 Tobramicyn MIC50 of Pseudomonas aeruginosa at week 8
    End point description
    MIC50 values were calculated for three different Pseudomonas aeruginosa (PA) strains: - Morphotype 1: mucoid - Morphotype 2: dry - Morphotype 3: variant Overall MIC50 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal, then the MIC value for the isolate with the highest bacterial load value was used.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5).
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    129 [47]
    128 [48]
    Units: micrograms(mL
        number (not applicable)
    1
    1
    Notes
    [47] - this is the actual number of the patients analyzed
    [48] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Tobramicyn MIC90 of Pseudomonas aeruginosa at week 4

    		 Close Top of page
    End point title
    		 Tobramicyn MIC90 of Pseudomonas aeruginosa at week 4
    End point description
    MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains: - Morphotype 1: mucoid - Morphotype 2: dry - Morphotype 3: variant Overall MIC90 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 4 (Visit 4).
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    126 [49]
    134 [50]
    Units: micrograms/mL
        number (not applicable)
    32
    32
    Notes
    [49] - this is the actual number of the patients analyzed
    [50] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Tobramicyn MIC90 of Pseudomonas aeruginosa at week 8

    		 Close Top of page
    End point title
    		 Tobramicyn MIC90 of Pseudomonas aeruginosa at week 8
    End point description
    MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains: - Morphotype 1: mucoid - Morphotype 2: dry - Morphotype 3: variant Overall MIC90 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Week 8 (Visit 5).
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    129 [51]
    128 [52]
    Units: micrograms/mL
        number (not applicable)
    32
    32
    Notes
    [51] - this is the actual number of the patients analyzed
    [52] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Microbiological outcome by visit

    		 Close Top of page
    End point title
    		 Microbiological outcome by visit
    End point description
    Microbiological outcomes are derived considering all P. aeruginosa (PA) morphotypes together. Week 4 and Week 8 microbiological outcomes: Eradication = elimination of PA Persistence = persistence of PA detected at previous visit Superinfection = appearance of a pathogen (other than PA) not detected at previous visit Re-infection (week 8 only) = re-appearance of PA detected at Screening and eradicated at Week 4 Superinfection supersedes eradication. Persistence for P. aeruginosa supersedes superinfection. Re-infection for P. aeruginosa supersedes superinfection.
    End point type
    Secondary
    End point timeframe
    Week 4 and Week 8
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    162 [53]
    Units: percentage of participants
    number (not applicable)
        Screening presence of P aeruginosa
    100
    100
        Week 4 - Eradication
    9.2
    7.1
        Week 4 - Persistence
    82.9
    85.3
        Week 4 - Superinfection
    7.9
    7.7
        Week 8 - Eradication
    2.7
    3.4
        Week 8 - Persistence
    78.9
    83
        Week 8 - Superinfection
    9.5
    9.5
        Week 8 - Reinfection
    8.8
    4.1
    Notes
    [53] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 2 in Body Weight

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 in Body Weight
    End point description
    Body weight was measured at all study visits as part of the physical examination
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Weeks 2 (Visit 3).
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    163
    Units: kilograms
        arithmetic mean (standard deviation)
    0.24 ( 0.68 )
    0.22 ( 0.72 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 4 in Body Weight

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 4 in Body Weight
    End point description
    Body weight was measured at all study visits as part of the physical examination.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Weeks 4 (Visit 4). For Visit 4, LOCF values are reported.
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    163
    Units: kilograms
        arithmetic mean (standard deviation)
    0.4 ( 0.9 )
    0.39 ( 1.01 )
    Statistical analysis title
    		 CHF1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF) values.
    Comparison groups
    TOBI - ITT Population v CHF 1538 - ITT Population
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 other [54]
    P-value
    		 = 0.886 [55]
    Method
    		 ANCOVA
    Parameter type
    		 least Square Means Difference
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.23
    Notes
    [54] - Change from baseline in weight was analyzed at Visit 4 by an ANCOVA model including treatment, country, sex and age in classes (6-12 years, 13-17 years, > 17 years) as factors and baseline value as covariate.
    [55] - the p value reported here refers to the "treatment" as effect/factor.

    Secondary: Change From Baseline to End of Week 8 in Body Weight

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 in Body Weight
    End point description
    Body weight was measured at all study visits as part of the physical examination.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Weeks 8 (Visit 5),
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    155 [56]
    159
    Units: KIlograms
        arithmetic mean (standard deviation)
    0.6 ( 1.14 )
    0.53 ( 1.27 )
    Notes
    [56] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 2 in Body Mass Index (BMI)

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 2 in Body Mass Index (BMI)
    End point description
    BMI was measured at all study visits as part of the physical examination.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Weeks 2 (Visit 3),
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    163
    Units: kilograms/meters^2
        arithmetic mean (standard deviation)
    0.1 ( 0.28 )
    0.1 ( 0.29 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to End of Week 4 in Body Mass Index (BMI)

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 4 in Body Mass Index (BMI)
    End point description
    BMI was measured at all study visits as part of the physical examination.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Weeks 4 (Visit 4). For Visit 4, LOCF values are reported.
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    158
    163
    Units: kilograms/meters^2
        arithmetic mean (standard deviation)
    0.12 ( 0.37 )
    0.12 ( 0.39 )
    Statistical analysis title
    		 CHF1538 vs TOBI
    Statistical analysis description
    This statistical analysis is based on last observation carried forward (LOCF) values.
    Comparison groups
    CHF 1538 - ITT Population v TOBI - ITT Population
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 other [57]
    P-value
    		 = 0.856 [58]
    Method
    		 ANCOVA
    Parameter type
    		 least Square Means Difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.08
    Notes
    [57] - Change from baseline in BMI was analyzed at Visit 4 by an ANCOVA model including treatment, country, sex and age in classes (6-12 years, 13-17 years, > 17 years) as factors and baseline value as covariate.
    [58] - the p value reported here refers to the "treatment" as effect/factor.

    Secondary: Change From Baseline to End of Week 8 in Body Mass Index (BMI)

    		 Close Top of page
    End point title
    		 Change From Baseline to End of Week 8 in Body Mass Index (BMI)
    End point description
    BMI was measured at all study visits as part of the physical examination.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 2), Weeks 8 (Visit 5),
    End point values
    		 CHF 1538 - ITT Population TOBI - ITT Population
    Number of subjects analysed
    155 [59]
    159 [60]
    Units: kilograms/meters^2
        arithmetic mean (standard deviation)
    0.16 ( 0.48 )
    0.14 ( 0.49 )
    Notes
    [59] - this is the actual number of the patients analyzed
    [60] - this is the actual number of the patients analyzed
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Day 0 to Week 8
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.0
    Reporting groups
    Reporting group title
    CHF1538
    Reporting group description
    		 tobramycin / Bramitob administered 300mg twice a day for 4 weeks

    Reporting group title
    TOBI
    Reporting group description
    		 tobramycin / TOBI administered 300mg twice a day for 4 weeks

    Serious adverse events
    		 CHF1538 TOBI
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 156 (3.85%)
    2 / 168 (1.19%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Cystic fibrosis lung
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 168 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0.6%
    Non-serious adverse events
    		 CHF1538 TOBI
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 156 (28.21%)
    47 / 168 (27.98%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Catheter site phlebitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Chest discomfort
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Chest pain
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Face oedema
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    2 / 156 (1.28%)
    0 / 168 (0.00%)
         occurrences all number
    6
    0
    Mucosal dryness
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    5 / 156 (3.21%)
    5 / 168 (2.98%)
         occurrences all number
    5
    5
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    10 / 156 (6.41%)
    10 / 168 (5.95%)
         occurrences all number
    12
    11
    Dysphonia
         subjects affected / exposed
    1 / 156 (0.64%)
    2 / 168 (1.19%)
         occurrences all number
    2
    2
    Haemoptysis
         subjects affected / exposed
    3 / 156 (1.92%)
    2 / 168 (1.19%)
         occurrences all number
    3
    2
    Nasal congestion
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    3 / 156 (1.92%)
    1 / 168 (0.60%)
         occurrences all number
    3
    1
    Productive cough
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Rales
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Sputum increased
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Audiogram abnormal
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 168 (0.60%)
         occurrences all number
    1
    1
    Blood glucose increased
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Forced expiratory volume decreased
         subjects affected / exposed
    2 / 156 (1.28%)
    1 / 168 (0.60%)
         occurrences all number
    2
    1
    Neutrophil count increased
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Pulmonary function test decreased
         subjects affected / exposed
    0 / 156 (0.00%)
    2 / 168 (1.19%)
         occurrences all number
    0
    2
    Red blood cell sedimentation rate increased
         subjects affected / exposed
    1 / 156 (0.64%)
    3 / 168 (1.79%)
         occurrences all number
    1
    3
    Injury, poisoning and procedural complications
    Skin injury
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Congenital, familial and genetic disorders
    Cystic fibrosis lung
         subjects affected / exposed
    5 / 156 (3.21%)
    4 / 168 (2.38%)
         occurrences all number
    5
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    5 / 156 (3.21%)
    0 / 168 (0.00%)
         occurrences all number
    6
    0
    Somnolence
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Deafness neurosensory
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Hypoacusis
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 168 (0.60%)
         occurrences all number
    1
    1
    Otosalpingitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    2 / 156 (1.28%)
    0 / 168 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Back pain
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    acute tonsillitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    3 / 156 (1.92%)
    3 / 168 (1.79%)
         occurrences all number
    3
    3
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Lung infection
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    6 / 156 (3.85%)
    2 / 168 (1.19%)
         occurrences all number
    6
    2
    Pharyngitis
         subjects affected / exposed
    6 / 156 (3.85%)
    2 / 168 (1.19%)
         occurrences all number
    6
    2
    Pneumonia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 156 (0.64%)
    1 / 168 (0.60%)
         occurrences all number
    1
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 156 (0.64%)
    3 / 168 (1.79%)
         occurrences all number
    1
    4
    Rhinitis
         subjects affected / exposed
    7 / 156 (4.49%)
    5 / 168 (2.98%)
         occurrences all number
    7
    5
    Sinusitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Tracheitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Tracheobronchitis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 156 (1.28%)
    3 / 168 (1.79%)
         occurrences all number
    2
    3
    Varicella
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Viral pharyngitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 168 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 168 (0.60%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Dec 2008
    Version 3 of the Protocol incorporates Version 2 and the amendment (substantial general amendment 1.0) which contains substantial changes to the trial conduct and design.

    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 limitation or caveats to this summary of results.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/24464974
    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-Fri Apr 26 22:47:29 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA