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 randomized, multi-center, parallel group, double-blind, placebo and formoterol controlled 14 day dose ranging trial of 4 doses of indacaterol delivered via Twisthaler®, in adult and adolescent patients with persistent asthma

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2007-003191-19
    Trial protocol
    		 BE   CZ   ES   HU   GB   PL   SK   DE  
    Global end of trial date
    18 Apr 2008

    Results information
    Results version number
    		 v2(current)
    This version publication date
    08 Jul 2016
    First version publication date
    07 Aug 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Corrected P-value in primary outcome measure for the comparison of Formoterol 12 μg v Indacaterol 500 μg

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CQMF149A2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00545272
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Apr 2008
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Apr 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the trial was to evaluate the dose response relationship among four doses of indacaterol treatment (62.5, 125, 250, and 500 micrograms [μg]) administered once daily (o.d.) and placebo as measured by the mean change from baseline to 24 hours (post-dose) trough forced expiratory volume (FEV1) after 14 days of treatment.
    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. Inhaled short acting β 2 -agonist (100 µg/ 90 µg salbutamol/albuterol) metered dose inhaler (MDI) or dry powder inhaler (DPI) formulation was allowed as rescue medication. Subjects were instructed to abstain from taking rescue salbutamol/ albuterol within the 6 hours of the start of each visit unless absolutely necessary. The investigator provided follow-up medical care for all subjects who were prematurely withdrawn from the study, or referred them for appropriate ongoing care.
    Background therapy
    		 Subjects who were using a long acting β2-agonist (LABA) prior screening were moved to short acting β2-agonists (SABA) treatment as needed. Subjects who were using fixed-dose combinations, used inhaled corticosteroid monotherapy in addition to SABA as needed as background therapy in the study.
    Evidence for comparator
    		 Formoterol fumarate, an approved medication for the treatment of subjects with asthma was used as an active comparator group in this study. Subjects were required to use inhaled corticosteroid at the standard recommended dose (12 µg twice daily) for the duration of the study.
    Actual start date of recruitment
    05 Oct 2007
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 82
    Country: Number of subjects enrolled
    Slovakia: 11
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    United Kingdom: 36
    Country: Number of subjects enrolled
    Belgium: 61
    Country: Number of subjects enrolled
    Czech Republic: 56
    Country: Number of subjects enrolled
    Germany: 26
    Country: Number of subjects enrolled
    Hungary: 40
    Country: Number of subjects enrolled
    South Africa: 35
    Country: Number of subjects enrolled
    Israel: 38
    Worldwide total number of subjects
    392
    EEA total number of subjects
    319
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    25
    Adults (18-64 years)
    332
    From 65 to 84 years
    35
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 49 centres in 10 countries.

    Pre-assignment
    Screening details
    		 A total of 583 subjects were screened, of which 392 subjects were randomized into the study.

    Period 1
    Period 1 title
    Double-blind Treatment Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    The identity of the active and placebo treatments was concealed by the use of study drugs that were all identical in packaging, labeling, schedule of administration and appearance. A double-dummy design was used because the inhalers required for the administration of active comparator and experimental treatments were different. Unblinding was allowed in the case of subject emergencies, and at the conclusion of the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Indacaterol 62.5 μg
    Arm description
    		 Subjects received indacaterol 62.5 μg o.d., and placebo to formoterol twice daily (b.i.d.) for 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Indacaterol
    Investigational medicinal product code
    QMF149
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Indacaterol 62.5 μg was delivered by the Twisthaler device o.d. for 14 days

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo to formoterol was delivered by the Aerolizer device b.i.d. for 14 days.

    Arm title
    		 Indacaterol 125 μg
    Arm description
    		 Subjects received indacaterol 125 μg o.d., and placebo to formoterol twice daily for 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Indacaterol
    Investigational medicinal product code
    QMF149
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Indacaterol 125 μg was delivered by the Twisthaler device o.d. for 14 days

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo to formoterol was delivered by the Aerolizer device twice daily for 14 days.

    Arm title
    		 Indacaterol 250 μg
    Arm description
    		 Subjects received indacaterol 250 μg o.d., and placebo to formoterol b.i.d. for 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Indacaterol
    Investigational medicinal product code
    QMF149
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Indacaterol 250 μg was delivered by the Twisthaler device o.d. for 14 days

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo to formoterol was delivered by the Aerolizer device b.i.d. for 14 days.

    Arm title
    		 Indacaterol 500 μg
    Arm description
    		 Subjects received indacaterol 500 μg o.d., and placebo to formoterol b.i.d. for 14 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Indacaterol
    Investigational medicinal product code
    QMF149
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Indacaterol 500 μg was delivered by the Twisthaler device o.d. for 14 days

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo to formoterol was delivered by the Aerolizer device b.i.d. for 14 days.

    Arm title
    		 Formoterol 12 μg
    Arm description
    		 Subjects received formoterol 12 μg b.i.d., and placebo to indacaterol o.d. for 14 days.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Formoterol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Formoterol 12 μg was delivered by the Aerolizer device b.i.d. for 14 days.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo to indacaterol was delivered by the Twisthaler device o.d. for 14 days.

    Arm title
    		 Placebo
    Arm description
    		 Subjects received placebo to indacaterol o.d., and placebo to formoterol twice daily for 14 days.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo to indacaterol was delivered by the Twisthaler device o.d. for 14 days.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, hard capsule
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo to formoterol was delivered by the Aerolizer device b.i.d. for 14 days.

    Number of subjects in period 1
    		Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo
    Started
    61
    68
    65
    72
    64
    62
    Completed
    61
    67
    64
    71
    62
    59
    Not completed
    0
    1
    1
    1
    2
    3
         Adverse event, non-fatal
    -
    -
    1
    -
    -
    1
         Abnormal laboratory value
    -
    -
    -
    -
    -
    1
         Lost to follow-up
    -
    -
    -
    -
    1
    -
         Abnormal test procedure result
    -
    -
    -
    -
    1
    -
         Protocol deviation
    -
    1
    -
    1
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Indacaterol 62.5 μg
    Reporting group description
    		 Subjects received indacaterol 62.5 μg o.d., and placebo to formoterol twice daily (b.i.d.) for 14 days.

    Reporting group title
    Indacaterol 125 μg
    Reporting group description
    		 Subjects received indacaterol 125 μg o.d., and placebo to formoterol twice daily for 14 days.

    Reporting group title
    Indacaterol 250 μg
    Reporting group description
    		 Subjects received indacaterol 250 μg o.d., and placebo to formoterol b.i.d. for 14 days.

    Reporting group title
    Indacaterol 500 μg
    Reporting group description
    		 Subjects received indacaterol 500 μg o.d., and placebo to formoterol b.i.d. for 14 days.

    Reporting group title
    Formoterol 12 μg
    Reporting group description
    		 Subjects received formoterol 12 μg b.i.d., and placebo to indacaterol o.d. for 14 days.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received placebo to indacaterol o.d., and placebo to formoterol twice daily for 14 days.

    Reporting group values
    		 Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo Total
    Number of subjects
    		 61 68 65 72 64 62 392
    Age categorical
    Units: Subjects
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 41.3 ± 16.27 38.4 ± 17.25 36.6 ± 15.76 40.1 ± 15.47 44 ± 17.98 39.8 ± 15.82 -
    Gender categorical
    Units: Subjects
        Female
    		 28 37 36 39 27 37 204
        Male
    		 33 31 29 33 37 25 188

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Indacaterol 62.5 μg
    Reporting group description
    		 Subjects received indacaterol 62.5 μg o.d., and placebo to formoterol twice daily (b.i.d.) for 14 days.

    Reporting group title
    Indacaterol 125 μg
    Reporting group description
    		 Subjects received indacaterol 125 μg o.d., and placebo to formoterol twice daily for 14 days.

    Reporting group title
    Indacaterol 250 μg
    Reporting group description
    		 Subjects received indacaterol 250 μg o.d., and placebo to formoterol b.i.d. for 14 days.

    Reporting group title
    Indacaterol 500 μg
    Reporting group description
    		 Subjects received indacaterol 500 μg o.d., and placebo to formoterol b.i.d. for 14 days.

    Reporting group title
    Formoterol 12 μg
    Reporting group description
    		 Subjects received formoterol 12 μg b.i.d., and placebo to indacaterol o.d. for 14 days.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received placebo to indacaterol o.d., and placebo to formoterol twice daily for 14 days.

    Primary: Change from baseline in trough forced expiratory volume in 1 second (FEV1) at Day 14

    		 Close Top of page
    End point title
    		 Change from baseline in trough forced expiratory volume in 1 second (FEV1) at Day 14
    End point description
    The FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Baseline FEV1 was defined as the average of two FEV1 assessments taken at 50 minutes and 15 minutes before the first study drug administration. Trough FEV1 was defined as the mean of 2 FEV1 measurements at 23 hour 10 minutes and 23 hours 45 minutes post-dose. If one of these assessments was missing then the trough was equal to the non-missing assessment. Positive change from baseline in trough favored experimental treatment. The analysis was performed in Intent to treat (ITT) population, defined as all randomized subjects who had a baseline and at least one post-dose measurement.
    End point type
    Primary
    End point timeframe
    Day 1 Baseline (prior to first dose), Day 15 (24 hours after last dose)
    End point values
    		 Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo
    Number of subjects analysed
    60
    67
    63
    68
    62
    58
    Units: litres (L)
        least squares mean (standard error)
    0.039 ± 0.0408
    0.054 ± 0.0383
    0.124 ± 0.0401
    0.166 ± 0.0381
    0.075 ± 0.0405
    -0.018 ± 0.0415
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol versus Placebo)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Placebo v Indacaterol 62.5 μg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0298 [1]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.057
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.051
         upper limit
    		 0.165
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0547
    Notes
    [1] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol versus Placebo)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Placebo v Indacaterol 125 μg
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.176 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.072
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.033
         upper limit
    		 0.177
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0533
    Notes
    [2] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol versus Placebo)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Placebo v Indacaterol 250 μg
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.009 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.142
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.036
         upper limit
    		 0.248
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0541
    Notes
    [3] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol versus Placebo)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Placebo v Indacaterol 500 μg
    Number of subjects included in analysis
    126
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.184
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.08
         upper limit
    		 0.289
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0531
    Notes
    [4] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol versus Placebo)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Placebo v Formoterol 12 μg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.086 [5]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.093
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.013
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0543
    Notes
    [5] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol vs formoterol)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Indacaterol 62.5 μg v Formoterol 12 μg
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.499 [6]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.036
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.142
         upper limit
    		 0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0539
    Notes
    [6] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol vs formoterol)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Formoterol 12 μg v Indacaterol 125 μg
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.687 [7]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.021
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.124
         upper limit
    		 0.082
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0524
    Notes
    [7] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol vs formoterol)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Formoterol 12 μg v Indacaterol 250 μg
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.362 [8]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.049
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.056
         upper limit
    		 0.153
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0532
    Notes
    [8] - p-value was not adjusted for multiplicity.
    Statistical analysis title
    		 Change in trough FEV1 (Indacaterol vs formoterol)
    Statistical analysis description
    Change from baseline to (24 hour post dose) trough FEV1 (L) was analyzed using Analysis of Covariance ANCOVA adjusting for treatment and region with baseline FEV1 as a covariate
    Comparison groups
    Formoterol 12 μg v Indacaterol 500 μg
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.082 [9]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.091
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.012
         upper limit
    		 0.194
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0523
    Notes
    [9] - p-value was not adjusted for multiplicity.

    Secondary: Change from baseline in trough forced expiratory volume in 1 second (FEV1) at Day 1

    		 Close Top of page
    End point title
    		 Change from baseline in trough forced expiratory volume in 1 second (FEV1) at Day 1
    End point description
    The FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Baseline FEV1 was defined as the average of two FEV1 assessments taken at 50 minutes and 15 minutes before the first study drug administration. Trough FEV1 was defined as the mean of 2 FEV1 measurements at 23 hour 10 minutes and 23 hours 45 minutes post-dose. If one of these assessments was missing then the trough was equal to the non-missing assessment. Positive change from baseline in trough favored experimental treatment. The analysis was perfumed in ITT population.
    End point type
    Secondary
    End point timeframe
    Day 1 baseline (prior to first-dose), Day 1 (24 hours post first-dose)
    End point values
    		 Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo
    Number of subjects analysed
    61
    68
    64
    69
    63
    62
    Units: Litres
        least squares mean (standard error)
    0.054 ± 0.0347
    0.081 ± 0.0326
    0.143 ± 0.0339
    0.141 ± 0.0326
    0.155 ± 0.0341
    0.01 ± 0.0344
    No statistical analyses for this end point

    Secondary: Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14

    		 Close Top of page
    End point title
    		 Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14
    End point description
    FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 was calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1, which is taken as the maximum FEV1 recorded post-dose. The analysis was performed in the ITT population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 14 (pre-dose and up to 4 hours post-dose)
    End point values
    		 Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo
    Number of subjects analysed
    61
    68
    65
    72
    64
    62
    Units: minutes
    arithmetic mean (standard deviation)
        Day 1 (n= 61, 68, 65, 71, 64, 62)
    91 ± 83.02
    109.6 ± 81.09
    119 ± 81.64
    116.2 ± 75.5
    105.6 ± 70.64
    90.5 ± 82.46
        Day 14 (n=61, 66, 64, 70, 62, 59)
    103.8 ± 86.67
    118.7 ± 88.42
    96.7 ± 70.65
    114 ± 76.41
    114.6 ± 71.64
    80.4 ± 76.92
    No statistical analyses for this end point

    Secondary: Forced Expiratory Volume in 1 Second (FEV1) area under the curve from baseline to 4 hours post-dose (AUC 0-4) on Day 1 and Day 14

    		 Close Top of page
    End point title
    		 Forced Expiratory Volume in 1 Second (FEV1) area under the curve from baseline to 4 hours post-dose (AUC 0-4) on Day 1 and Day 14
    End point description
    FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 AUC (0-4) was evaluated for subjects with complete or incomplete FEV1 assessments, based on the observed FEV1 measurements. The missing FEV1 measurements were not interpolated. The analyses was performed in ITT population and accounted all subjects with at least one FEV1 assessment between baseline (pre-dose) and 4 hours post-dose. Here 'n' signifies those subjects evaluable for the outcome measure, at specified time-points, respectively.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 14 (pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose)
    End point values
    		 Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo
    Number of subjects analysed
    61
    68
    65
    72
    64
    62
    Units: Litres
    least squares mean (standard error)
        Day 1 (n=61, 68, 65, 71, 64, 62)
    2.668 ± 0.0281
    2.687 ± 0.0264
    2.726 ± 0.0272
    2.753 ± 0.0259
    2.832 ± 0.0274
    2.547 ± 0.0279
        Day 14 (n=61, 66, 64, 69, 62, 59)
    2.67 ± 0.0419
    2.698 ± 0.04
    2.772 ± 0.0411
    2.786 ± 0.0393
    2.821 ± 0.0418
    2.565 ± 0.0426
    No statistical analyses for this end point

    Secondary: Change From Baseline in Morning and Evening Peak Expiratory Flow at Day 14

    		 Close Top of page
    End point title
    		 Change From Baseline in Morning and Evening Peak Expiratory Flow at Day 14
    End point description
    The Peak Expiratory Flow (PEF) is a convenient for monitoring of airway function at home, and it is commonly used to assess response to treatment or to document diurnal variation. PEF rate is the maximal rate that a person can exhale during a short maximal expiratory effort after fully inhaling. The PEF was measured using a peak flow meter every morning and evening during the study, prior administration of study medication, except evenings on the day of clinic visits. Change from baseline was the difference between the mean baseline PEF recorded during the screening period until the first day of treatment, and the overall mean PEF from Day 1 to 14. The analysis was performed in ITT population. Here ‘n’ signifies those subjects evaluable for this measure at specified time-points, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline (screening period), Day 1 up to Day 14 (treatment period)
    End point values
    		 Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo
    Number of subjects analysed
    61
    68
    65
    72
    64
    62
    Units: Litres/minute
    arithmetic mean (standard deviation)
        Morning PEF (n=56, 61, 53, 63, 57, 48)
    18.7 ± 29.28
    17.2 ± 34.07
    25.7 ± 38.37
    25.8 ± 47.36
    25.2 ± 38.28
    -4.3 ± 43
        Evening PEF (n=56, 58, 54, 59, 55, 47)
    5.9 ± 36.92
    4.2 ± 37.82
    18.4 ± 36.7
    25.8 ± 38.07
    26.2 ± 35.01
    -11.4 ± 50.73
    No statistical analyses for this end point

    Secondary: Number of subjects using rescue medication during day and night

    		 Close Top of page
    End point title
    		 Number of subjects using rescue medication during day and night
    End point description
    Subjects recorded the use of rescue medications (salbutamol/albuterol) for treatment of asthma symptoms in a diary during day and night. Rescue medication during the day time was defined as number of puffs of rescue medication used in the 6 hours prior to evening PEF measurement. Rescue medication during the night time was defined as number of puffs of rescue medication used in the 12 hours prior recording the morning PEF measurement. The analysis was performed in ITT population.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 14
    End point values
    		 Indacaterol 62.5 μg Indacaterol 125 μg Indacaterol 250 μg Indacaterol 500 μg Formoterol 12 μg Placebo
    Number of subjects analysed
    61
    68
    65
    72
    64
    62
    Units: Subjects
    number (not applicable)
        Day
    33
    43
    28
    35
    30
    39
        Night
    36
    40
    36
    34
    31
    40
    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 are reported in this record from First Patient First Treatment until Last Patient Last Visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    11.0
    Reporting groups
    Reporting group title
    Indacaterol 62.5 µg
    Reporting group description
    		 Indacaterol 62.5 µg

    Reporting group title
    Indacaterol 125 µg
    Reporting group description
    		 Indacaterol 125 µg

    Reporting group title
    Indacaterol 250 µg
    Reporting group description
    		 Indacaterol 250 µg

    Reporting group title
    Indacaterol 500 µg
    Reporting group description
    		 Indacaterol 500 µg

    Reporting group title
    Formoterol 12 µg
    Reporting group description
    		 Formoterol 12 µg

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Serious adverse events
    		 Indacaterol 62.5 µg Indacaterol 125 µg Indacaterol 250 µg Indacaterol 500 µg Formoterol 12 µg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 68 (0.00%)
    0 / 65 (0.00%)
    0 / 72 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthmatic crisis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 68 (0.00%)
    0 / 65 (0.00%)
    0 / 72 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         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: 2%
    Non-serious adverse events
    		 Indacaterol 62.5 µg Indacaterol 125 µg Indacaterol 250 µg Indacaterol 500 µg Formoterol 12 µg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 61 (6.56%)
    6 / 68 (8.82%)
    8 / 65 (12.31%)
    14 / 72 (19.44%)
    3 / 64 (4.69%)
    3 / 62 (4.84%)
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 68 (0.00%)
    0 / 65 (0.00%)
    2 / 72 (2.78%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Headache
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 68 (1.47%)
    2 / 65 (3.08%)
    2 / 72 (2.78%)
    2 / 64 (3.13%)
    2 / 62 (3.23%)
         occurrences all number
    2
    1
    2
    2
    2
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 68 (2.94%)
    4 / 65 (6.15%)
    8 / 72 (11.11%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    2
    2
    4
    8
    0
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 68 (2.94%)
    0 / 65 (0.00%)
    1 / 72 (1.39%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    0
    3
    0
    1
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 68 (1.47%)
    2 / 65 (3.08%)
    1 / 72 (1.39%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences all number
    0
    1
    2
    1
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Jul 2007
    The protocol was amended for compliance with national regulations or clinical practice concerning the inclusion of subjects less than 18 years of age in clinical trials and time frame for collection of AEs was modified to start after administration of first dose of study treatments.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 27 04:52:41 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA