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    Clinical Trial Results:
    A 52-week, multicenter, randomized, double-blind, placebocontrolled study to assess the efficacy and safety of QAW039 when added to existing asthma therapy in patients with uncontrolled severe asthma

    Summary
    EudraCT number
    2015-002553-35
    Trial protocol
    GB   HU   AT   DE   EE   LV   BE   IS   FI   DK   FR   PL   LT   IE   ES   GR  
    Global end of trial date
    04 Nov 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    20 May 2020
    First version publication date
    20 May 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CQAW039A2307
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02555683
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Novartis Pharmaceuticals
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharmaceuticals, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharmaceuticals, 41 613241111, Novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Nov 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Nov 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary objectives: In patients with severe asthma and high eosinophil counts (≥250 cells/μL) receiving standard-of-care asthma therapy: - To demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment period. In all patients with severe asthma receiving standard-of-care asthma therapy: - To demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment period.
    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.
    Background therapy
    All patients were provided with SABAs (Short-acting β2-agonist) (salbutamol/albuterol/other SABA) which they were instructed to use throughout the study as rescue medication on an ‘as needed basis’.
    Evidence for comparator
    -
    Actual start date of recruitment
    11 Dec 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 11
    Country: Number of subjects enrolled
    Australia: 14
    Country: Number of subjects enrolled
    Belgium: 24
    Country: Number of subjects enrolled
    Austria: 19
    Country: Number of subjects enrolled
    Brazil: 44
    Country: Number of subjects enrolled
    China: 60
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    Estonia: 12
    Country: Number of subjects enrolled
    Finland: 5
    Country: Number of subjects enrolled
    France: 50
    Country: Number of subjects enrolled
    Germany: 87
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Guatemala: 80
    Country: Number of subjects enrolled
    Hungary: 64
    Country: Number of subjects enrolled
    Latvia: 18
    Country: Number of subjects enrolled
    Lithuania: 18
    Country: Number of subjects enrolled
    Philippines: 34
    Country: Number of subjects enrolled
    Poland: 51
    Country: Number of subjects enrolled
    Romania: 154
    Country: Number of subjects enrolled
    Singapore: 5
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    United Kingdom: 31
    Country: Number of subjects enrolled
    United States: 85
    Country: Number of subjects enrolled
    Vietnam: 20
    Worldwide total number of subjects
    894
    EEA total number of subjects
    539
    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)
    29
    Adults (18-64 years)
    705
    From 65 to 84 years
    159
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    Participants were from Argentina, Australia, Austria, Belgium, Brazil, China, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Hungary, Latvia, Lithuania, Philippines, Poland, Romania, Singapore, Spain, Switzerland, UK, US, Vietnam.

    Pre-assignment
    Screening details
    The study included a Screening period of up to 2 weeks and a Placebo Run-in period of 2 to 6 weeks, during which eligibility for randomization was determined.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    QAW039 150 mg
    Arm description
    QAW039 150 mg once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Fevipiprant
    Investigational medicinal product code
    QAW039
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    QAW039 150 mg once daily (one tablet of blinded QAW039 at 150 mg dosage strength given together with one tablet blinded placebo to QAW039 450 mg)

    Arm title
    QAW039 450 mg
    Arm description
    QAW039 450 mg once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Fevipiprant
    Investigational medicinal product code
    QAW039
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    QAW039 450 mg once daily (one tablet of blinded QAW039 at 450 mg dosage strength given together with one tablet blinded placebo to QAW039 150 mg)

    Arm title
    Placebo
    Arm description
    Placebo once daily
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to QAW039 once daily (one tablet blinded placebo to QAW039 150 mg and one tablet blinded placebo to QAW039 450 mg)

    Number of subjects in period 1
    QAW039 150 mg QAW039 450 mg Placebo
    Started
    301
    295
    298
    FAS/SAF: High eosinophil subpopulation
    200 [1]
    201 [2]
    201 [3]
    FAS/SAF: Overall population
    299
    293
    298
    Completed
    282
    278
    269
    Not completed
    19
    17
    29
         Death post Treatment/safety period
    -
    1
    -
         Physician decision
    1
    -
    2
         Lack of efficacy
    2
    -
    -
         Adverse event, serious fatal
    -
    1
    2
         Adverse event, non-fatal
    1
    -
    1
         Protocol deviation
    -
    1
    -
         Technical Problems
    1
    1
    -
         Subject/guardian decision
    12
    12
    22
         Lost to follow-up
    2
    1
    2
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The numbers descrived disposition data for subpopulation
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The numbers descrived disposition data for subpopulation
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The numbers descrived disposition data for subpopulation

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    QAW039 150 mg
    Reporting group description
    QAW039 150 mg once daily

    Reporting group title
    QAW039 450 mg
    Reporting group description
    QAW039 450 mg once daily

    Reporting group title
    Placebo
    Reporting group description
    Placebo once daily

    Reporting group values
    QAW039 150 mg QAW039 450 mg Placebo Total
    Number of subjects
    301 295 298 894
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    14 7 8 29
        Adults (18-64 years)
    239 230 236 705
        From 65-84 years
    48 57 54 159
        85 years and over
    0 1 0 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    49.9 ± 14.97 51.1 ± 14.29 50.3 ± 14.48 -
    Sex: Female, Male
    Units: Participants
        Female
    192 214 177 583
        Male
    109 81 121 311
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    214 215 213 642
        Black
    11 6 12 29
        Asian
    45 38 44 127
        Native American
    24 29 24 77
        Unknown
    1 2 3 6
        Other
    6 5 2 13

    End points

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    End points reporting groups
    Reporting group title
    QAW039 150 mg
    Reporting group description
    QAW039 150 mg once daily

    Reporting group title
    QAW039 450 mg
    Reporting group description
    QAW039 450 mg once daily

    Reporting group title
    Placebo
    Reporting group description
    Placebo once daily

    Primary: Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation

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    End point title
    Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation
    End point description
    A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
    End point type
    Primary
    End point timeframe
    Baseline, Week 52
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    200 [1]
    201 [2]
    201 [3]
    Units: events/year
        least squares mean (confidence interval 95%)
    0.97 (0.78 to 1.20)
    0.77 (0.62 to 0.97)
    0.93 (0.75 to 1.16)
    Notes
    [1] - High eosinophil subpopulation
    [2] - High eosinophil subpopulation
    [3] - High eosinophil subpopulation
    Statistical analysis title
    Regression
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    401
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8 [4]
    Method
    negative binomial regression model
    Parameter type
    rate ratio
    Point estimate
    1.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.77
         upper limit
    1.41
    Notes
    [4] - adjusted p-value
    Statistical analysis title
    Regression
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    402
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.51 [5]
    Method
    negative binomial regression model
    Parameter type
    Rate Ratio
    Point estimate
    0.83
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.61
         upper limit
    1.14
    Notes
    [5] - adjusted p-value

    Primary: Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall population

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    End point title
    Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall population
    End point description
    A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours).
    End point type
    Primary
    End point timeframe
    Baseline, Week 52
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    299
    293
    298
    Units: events/year
        least squares mean (confidence interval 95%)
    0.92 (0.77 to 1.09)
    0.75 (0.62 to 0.90)
    0.96 (0.80 to 1.15)
    Statistical analysis title
    Regression
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    597
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.819 [6]
    Method
    negative binomial regression model
    Parameter type
    rate ratio
    Point estimate
    0.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.75
         upper limit
    1.22
    Notes
    [6] - adjusted p-value
    Statistical analysis title
    Regression
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.51 [7]
    Method
    negative binomial regression model
    Parameter type
    Rate Ratio
    Point estimate
    0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.61
         upper limit
    1.01
    Notes
    [7] - adjusted p-value

    Secondary: Change from baseline to week 52 in Asthma Quality of Life Questionnaire for Participants 12 years and older (AQLQ+12) score in high eosinophils subpopulation

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    End point title
    Change from baseline to week 52 in Asthma Quality of Life Questionnaire for Participants 12 years and older (AQLQ+12) score in high eosinophils subpopulation
    End point description
    The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    200 [8]
    201 [9]
    201 [10]
    Units: units on scale
        least squares mean (standard error)
    0.75 ± 0.067
    0.81 ± 0.067
    0.68 ± 0.067
    Notes
    [8] - High eosinophil subpopulation
    [9] - High eosinophil subpopulation
    [10] - High eosinophil subpopulation
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    401
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.819 [11]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.11
         upper limit
    0.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.095
    Notes
    [11] - adjusted p-value
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    402
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.591 [12]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    0.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.095
    Notes
    [12] - adjusted p-vale

    Secondary: Change from Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) score in high eosinophils subpopulation

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    End point title
    Change from Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) score in high eosinophils subpopulation
    End point description
    The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    200 [13]
    201 [14]
    201 [15]
    Units: units on scale
        least squares mean (standard error)
    -0.88 ± 0.069
    -0.94 ± 0.069
    -0.76 ± 0.070
    Notes
    [13] - High eosinophil subpopulation
    [14] - High eosinophil subpopulation
    [15] - High eosinophil subpopulation
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    401
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.819 [16]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -0.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.31
         upper limit
    0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.098
    Notes
    [16] - adjusted p-value
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    402
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.591 [17]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -0.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.37
         upper limit
    0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.098
    Notes
    [17] - adjusted p-value

    Secondary: Change from Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 second (FEV1) in high eosinophils subpopulation

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    End point title
    Change from Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 second (FEV1) in high eosinophils subpopulation
    End point description
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    200 [18]
    201 [19]
    201 [20]
    Units: Liter
        least squares mean (standard error)
    0.169 ± 0.0257
    0.153 ± 0.0255
    0.103 ± 0.0260
    Notes
    [18] - High eosinophil subpopulation
    [19] - High eosinophil subpopulation
    [20] - High eosinophil subpopulation
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    401
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8 [21]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.067
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.005
         upper limit
    0.139
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0365
    Notes
    [21] - adjusted p-value
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    402
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.523 [22]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.021
         upper limit
    0.121
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0363
    Notes
    [22] - adjusted p-value

    Secondary: Change from baseline to week 52 in Asthma Quality of Life Questionnaire for Participants 12 years and older (AQLQ+12) score in overall population

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    End point title
    Change from baseline to week 52 in Asthma Quality of Life Questionnaire for Participants 12 years and older (AQLQ+12) score in overall population
    End point description
    The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    299
    293
    298
    Units: units on scale
        least squares mean (standard error)
    0.68 ± 0.053
    0.73 ± 0.054
    0.61 ± 0.054
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    597
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.819 [23]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.07
         upper limit
    0.23
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.076
    Notes
    [23] - adjusted p-value
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.591 [24]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.03
         upper limit
    0.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.076
    Notes
    [24] - adjusted p-vale

    Secondary: Change from Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) score in overall population

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    End point title
    Change from Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) score in overall population
    End point description
    The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    299
    293
    298
    Units: units on scale
        least squares mean (standard error)
    -0.83 ± 0.055
    -0.90 ± 0.056
    -0.71 ± 0.056
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    597
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.819 [25]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.27
         upper limit
    0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.079
    Notes
    [25] - adjusted p-value
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.591 [26]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -0.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.35
         upper limit
    -0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.079
    Notes
    [26] - adjusted p-value

    Secondary: Change from Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 second (FEV1) in overall population

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    End point title
    Change from Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 second (FEV1) in overall population
    End point description
    Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    QAW039 150 mg QAW039 450 mg Placebo
    Number of subjects analysed
    299
    293
    298
    Units: Liter
        least squares mean (standard error)
    0.144 ± 0.0205
    0.108 ± 0.0206
    0.068 ± 0.0209
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 150 mg v Placebo
    Number of subjects included in analysis
    597
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.819 [27]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.076
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.019
         upper limit
    0.134
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0292
    Notes
    [27] - adjusted p-value
    Statistical analysis title
    ANCOVA
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    591
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.591 [28]
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.017
         upper limit
    0.097
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0292
    Notes
    [28] - adjusted p-value

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs are presented from the first dose of study treatment until last dose plus 7 days. SAEs (including All-Cause Mortality) are presented from first dose of study treatment until last dose plus 30 days, up to a maximum duration of 56 weeks
    Adverse event reporting additional description
    Any sign or symptom that occurs during the study treatment plus 7 days post treatment for adverse events and 30 days post treatment for serious adverse events.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    QAW039 150 mg
    Reporting group description
    QAW039 150 mg

    Reporting group title
    Placebo
    Reporting group description
    Placebo

    Reporting group title
    QAW039 450 mg
    Reporting group description
    QAW039 450 mg

    Serious adverse events
    QAW039 150 mg Placebo QAW039 450 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    33 / 299 (11.04%)
    32 / 298 (10.74%)
    30 / 293 (10.24%)
         number of deaths (all causes)
    0
    2
    1
         number of deaths resulting from adverse events
    0
    1
    0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epithelioid mesothelioma
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leiomyosarcoma
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Testicular neoplasm
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Depression
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adnexa uteri cyst
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Electrocardiogram abnormal
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    10 / 299 (3.34%)
    14 / 298 (4.70%)
    8 / 293 (2.73%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 21
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasal polyps
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Essential tremor
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Superior sagittal sinus thrombosis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diaphragmatic hernia
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Megacolon
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal food impaction
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    2 / 293 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis chronic
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic spinal stenosis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial diarrhoea
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic hepatitis C
         subjects affected / exposed
    0 / 299 (0.00%)
    0 / 298 (0.00%)
    1 / 293 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 298 (0.34%)
    2 / 293 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 299 (1.00%)
    1 / 298 (0.34%)
    5 / 293 (1.71%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pneumonia chlamydial
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 298 (0.34%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 298 (0.00%)
    0 / 293 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    QAW039 150 mg Placebo QAW039 450 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    204 / 299 (68.23%)
    214 / 298 (71.81%)
    193 / 293 (65.87%)
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    13 / 299 (4.35%)
    9 / 298 (3.02%)
    11 / 293 (3.75%)
         occurrences all number
    15
    11
    15
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    151 / 299 (50.50%)
    155 / 298 (52.01%)
    135 / 293 (46.08%)
         occurrences all number
    345
    341
    299
    Cough
         subjects affected / exposed
    11 / 299 (3.68%)
    13 / 298 (4.36%)
    5 / 293 (1.71%)
         occurrences all number
    16
    20
    7
    Nervous system disorders
    Headache
         subjects affected / exposed
    28 / 299 (9.36%)
    24 / 298 (8.05%)
    22 / 293 (7.51%)
         occurrences all number
    53
    40
    28
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    16 / 299 (5.35%)
    11 / 298 (3.69%)
    16 / 293 (5.46%)
         occurrences all number
    19
    13
    16
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    29 / 299 (9.70%)
    26 / 298 (8.72%)
    22 / 293 (7.51%)
         occurrences all number
    42
    35
    37
    Lower respiratory tract infection
         subjects affected / exposed
    12 / 299 (4.01%)
    7 / 298 (2.35%)
    10 / 293 (3.41%)
         occurrences all number
    17
    8
    13
    Nasopharyngitis
         subjects affected / exposed
    43 / 299 (14.38%)
    49 / 298 (16.44%)
    37 / 293 (12.63%)
         occurrences all number
    63
    74
    50
    Rhinitis
         subjects affected / exposed
    8 / 299 (2.68%)
    12 / 298 (4.03%)
    11 / 293 (3.75%)
         occurrences all number
    9
    13
    11
    Sinusitis
         subjects affected / exposed
    18 / 299 (6.02%)
    18 / 298 (6.04%)
    19 / 293 (6.48%)
         occurrences all number
    25
    31
    22
    Upper respiratory tract infection
         subjects affected / exposed
    35 / 299 (11.71%)
    31 / 298 (10.40%)
    35 / 293 (11.95%)
         occurrences all number
    49
    47
    48
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    13 / 299 (4.35%)
    21 / 298 (7.05%)
    14 / 293 (4.78%)
         occurrences all number
    16
    23
    16
    Urinary tract infection
         subjects affected / exposed
    11 / 299 (3.68%)
    18 / 298 (6.04%)
    15 / 293 (5.12%)
         occurrences all number
    14
    19
    16
    Viral upper respiratory tract infection
         subjects affected / exposed
    29 / 299 (9.70%)
    26 / 298 (8.72%)
    26 / 293 (8.87%)
         occurrences all number
    40
    34
    34

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Aug 2015
    A literature review has identified additional statins that could interact with QAW039, and patients taking these statins were to be excluded from the study: Text was added to indicate that patients on doses of simvastatin >20 mg, doses of atorvastatin >40 mg, doses of pravastatin >40 mg, or doses of pitavastatin >2 mg per day should not be included in the study. Statin doses less than or equal to these doses as well as other statins were permitted during the study.
    19 May 2016
    Protocol changes were implemented as requested from health authorities and/or ethics committees/institutional review boards in some countries where the study was planned to be conducted. These changes included: • Changed inclusion criterion #2 to allow for the lower age limit in the study to patients aged ≥12 years (or ≥ lower age limit allowed by health authority and/or ethics committee/institutional review board approvals). • Added an exclusion criterion for patients below the 3rd percentile for weight by age for adolescent patients aged 12 to <18 years to ensure malnourished adolescents were excluded. • Added an exclusion criterion for lactose and milk sensitivity since the placebo tablets include lactose. • Added an exclusion criterion for patients with a history of conditions other than asthma that could result in elevated eosinophils (e.g., hypereosinophilic syndromes, Churg-Strauss Syndrome, eosinophilic esophagitis) and exclude patients with known parasitic infestation within 6 months prior to Visit 1. • Added country-required local contraception language for certain countries.
    10 Feb 2017
    Protocol was amended to include updated renal guidelines and liver event and laboratory trigger definitions of Novartis. These changes included: • Updated definitions of urine events. • Updated follow-up requirements for liver events and laboratory triggers for ALT and AST (> 3 to ≤ 5 × ULN [patient is asymptomatic]).

    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
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