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    Clinical Trial Results:
    A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Parallel Arm, Multi-Centre Study to Assess Efficacy and Safety of Multiple Dose Levels of AZD7594 DPI Given Once Daily for Twelve Weeks, Compared to Placebo, in Asthmatics Symptomatic on Low Dose ICS

    Summary
    EudraCT number
    2017-002483-40
    Trial protocol
    DE   HU   BG   PL  
    Global end of trial date
    30 Sep 2019

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

    Trial information

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    Trial identification
    Sponsor protocol code
    D3741C00007
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03622112
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Södertälje, Södertälje, Sweden, 151 85
    Public contact
    Global Clinical Lead, AstraZeneca AB, 301 3985799, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca AB, 301 3985799, ClinicalTrialTransparency@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Nov 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Sep 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose Inhaled Corticosteroid (ICS)
    Protection of trial subjects
    The global study protocol, the country-specific protocols and all protocol amendments, including all versions of informed consent forms (ICFs) and any other written information and/or materials provided to the subjects were approved by an Independent Ethics Committee/Institutional Review Board (IEC/ IRB) in writing. This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice (ICH/ GCP), applicable regulatory requirements and the AstraZeneca policy on Bioethics.The applicable regulatory requirements in Japan were GCP for Trials on Drugs ((Ministry of Health, Labour and Welfare [MHLW] Ordinance No.28, 27 March 1997, partially revised by MHLW Ordinance and their related notifications). Before signing the ICF, each subject was given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study. Every subject was given the opportunity to ask questions and allowed time to consider the information provided and was notified that he/she was free to discontinue from the study at any time.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Jan 2019
    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
    United States: 135
    Country: Number of subjects enrolled
    Japan: 82
    Country: Number of subjects enrolled
    Poland: 142
    Country: Number of subjects enrolled
    Ukraine: 125
    Country: Number of subjects enrolled
    Germany: 120
    Country: Number of subjects enrolled
    Hungary: 99
    Country: Number of subjects enrolled
    Bulgaria: 85
    Country: Number of subjects enrolled
    South Africa: 18
    Worldwide total number of subjects
    806
    EEA total number of subjects
    446
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    630
    From 65 to 84 years
    176
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted in 92 sites in 8 countries; Bulgaria, Germany, Hungary, Poland, and Ukraine, United States (US), South Africa, and Japan. In this study, 806 subjects (including 82 Japanese subjects) were randomised. For sites in the US, no subjects were randomised to the AZD7594 792 μg/720 μg once daily (QD) treatment arm.

    Pre-assignment
    Screening details
    Subjects attended a Screening Visit within 28 days before receiving their first dose. All subjects underwent inclusion exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures.

    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
    AZD7594 50 μg
    Arm description
    Oral inhalation of AZD5794 55 μg/ 50 μg (nominal dose/delivered dose) once daily (QD).
    Arm type
    Experimental

    Investigational medicinal product name
    AZD7594
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Oral use
    Dosage and administration details
    55 μg/50 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, dry powder inhaler (DPI)) QD

    Arm title
    AZD7594 90 μg
    Arm description
    Oral inhalation of AZD5794 99 μg/ 90 μg (nominal dose/delivered dose) once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD7594
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Oral use
    Dosage and administration details
    99 μg/90 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD

    Arm title
    AZD7594 180 μg
    Arm description
    Oral inhalation of AZD5794 198 μg/ 180 μg (nominal dose/delivered dose) once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD7594
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Oral use
    Dosage and administration details
    198 μg/180 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD

    Arm title
    AZD7594 360 μg
    Arm description
    Oral inhalation of AZD5794 396 μg/ 360 μg (nominal dose/delivered dose) once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD7594
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Oral use
    Dosage and administration details
    396 μg/360 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD

    Arm title
    AZD7594 720 μg
    Arm description
    Oral inhalation of AZD5794 792 μg/ 720 μg (nominal dose/delivered dose) once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD7594
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Oral use
    Dosage and administration details
    792 μg/720 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD (US excluded)

    Arm title
    Placebo to AZD7594
    Arm description
    Oral inhalation of placebo to AZD7594 once daily.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo to AZD7594
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Oral use
    Dosage and administration details
    Matching Placebo to AZD7594, Oral inhalation (by SD3FL inhaler, DPI) QD

    Arm title
    Fluticasone furoate
    Arm description
    Oral inhalation of fluticasone furoate 100 μg once daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Fluticasone furoate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Oral use
    Dosage and administration details
    100 μg per nominal dose, Oral inhalation (by ELLIPTA inhaler, DPI) QD

    Number of subjects in period 1 [1]
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Started
    110
    112
    111
    113
    134
    113
    112
    Completed
    85
    92
    95
    91
    124
    71
    103
    Not completed
    25
    20
    16
    22
    10
    42
    9
         Adverse event, serious fatal
    -
    -
    -
    1
    -
    -
    -
         Consent withdrawn by subject
    6
    2
    4
    2
    1
    2
    2
         Adverse event, non-fatal
    6
    8
    4
    11
    4
    20
    2
         Study-specific withdrawal criteria
    10
    8
    7
    6
    4
    18
    4
         Lost to follow-up
    1
    1
    -
    -
    -
    -
    -
         Reason not specified
    -
    1
    -
    1
    1
    2
    1
         Protocol deviation
    2
    -
    1
    1
    -
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: One randomized subject did not receive treatment as the subject deviated from the protocol and was randomized in error.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    AZD7594 50 μg
    Reporting group description
    Oral inhalation of AZD5794 55 μg/ 50 μg (nominal dose/delivered dose) once daily (QD).

    Reporting group title
    AZD7594 90 μg
    Reporting group description
    Oral inhalation of AZD5794 99 μg/ 90 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 180 μg
    Reporting group description
    Oral inhalation of AZD5794 198 μg/ 180 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 360 μg
    Reporting group description
    Oral inhalation of AZD5794 396 μg/ 360 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 720 μg
    Reporting group description
    Oral inhalation of AZD5794 792 μg/ 720 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    Placebo to AZD7594
    Reporting group description
    Oral inhalation of placebo to AZD7594 once daily.

    Reporting group title
    Fluticasone furoate
    Reporting group description
    Oral inhalation of fluticasone furoate 100 μg once daily.

    Reporting group values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate Total
    Number of subjects
    110 112 111 113 134 113 112 805
    Age Categorical
    Units: Subjects
        <=18 years
    0 0 0 0 0 0 0 0
        Between 18 and 65 years
    90 92 79 92 107 87 82 629
        >=65 years
    20 20 32 21 27 26 30 176
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    52.2 ± 12.8 53.2 ± 13.3 54.6 ± 14.5 52.8 ± 13.2 52.2 ± 13.0 53.4 ± 13.7 53.7 ± 13.4 -
    Sex: Female, Male
    Units: Subjects
        Female
    59 66 72 64 79 68 59 467
        Male
    51 46 39 49 55 45 53 338
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 1 0 0 0 0 0 1
        Asian
    9 11 10 13 16 13 12 84
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0 0 0
        Black or African American
    5 5 5 2 1 5 7 30
        White
    95 93 94 97 115 92 93 679
        More than one race
    1 2 2 1 2 3 0 11
        Unknown or Not Reported
    0 0 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    AZD7594 50 μg
    Reporting group description
    Oral inhalation of AZD5794 55 μg/ 50 μg (nominal dose/delivered dose) once daily (QD).

    Reporting group title
    AZD7594 90 μg
    Reporting group description
    Oral inhalation of AZD5794 99 μg/ 90 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 180 μg
    Reporting group description
    Oral inhalation of AZD5794 198 μg/ 180 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 360 μg
    Reporting group description
    Oral inhalation of AZD5794 396 μg/ 360 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 720 μg
    Reporting group description
    Oral inhalation of AZD5794 792 μg/ 720 μg (nominal dose/delivered dose) once daily.

    Reporting group title
    Placebo to AZD7594
    Reporting group description
    Oral inhalation of placebo to AZD7594 once daily.

    Reporting group title
    Fluticasone furoate
    Reporting group description
    Oral inhalation of fluticasone furoate 100 μg once daily.

    Primary: Change from baseline in trough Forced expiratory volume in 1 second (FEV1) at Week 12

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    End point title
    Change from baseline in trough Forced expiratory volume in 1 second (FEV1) at Week 12
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first investigational product (IP) administration (30 minutes apart, at −45 minutes and −15 minutes, before IP administration) on Day 1 (Visit 3). Analyses were based on a Mixed-effects model for repeated measures (MMRM) with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates.
    End point type
    Primary
    End point timeframe
    At Baseline and Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    83
    90
    92
    90
    123
    70
    103
    Units: Liters
        least squares mean (confidence interval 95%)
    -0.013 (-0.077 to 0.050)
    -0.031 (-0.094 to 0.031)
    0.062 (-0.001 to 0.124)
    0.099 (0.036 to 0.161)
    0.104 (0.046 to 0.162)
    0.022 (-0.046 to 0.091)
    0.133 (0.073 to 0.193)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.437
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.036
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.126
         upper limit
    0.054
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.236
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.054
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.143
         upper limit
    0.035
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.389
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.039
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    0.128
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.094
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.076
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.013
         upper limit
    0.165
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    193
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.06
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.082
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.003
         upper limit
    0.167
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.014
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.111
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.023
         upper limit
    0.199
    Notes
    [1] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in trough FEV1 at Weeks 2, 4, 8 and average over the Treatment Period

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    End point title
    Change from baseline in trough FEV1 at Weeks 2, 4, 8 and average over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period. Baseline was defined as the mean of the 2 measured values before first IP administration on Day 1. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. Analysis of covariance (ANCOVA) with treatment and region (ie, US, Japan, and Rest of the World [RoW]) as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. The reported number of subjects analysed corresponds to Week 2 and for Weeks 4, 8, 12 and average over the Treatment Period, the number of subjects analysed are provided as comment in the row titles.
    End point type
    Secondary
    End point timeframe
    At Baseline and Weeks 2, 4 and 8
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    108
    107
    108
    104
    132
    95
    109
    Units: Liters
    least squares mean (confidence interval 95%)
        Week 2
    0.018 (-0.038 to 0.073)
    0.011 (-0.044 to 0.066)
    0.067 (0.011 to 0.122)
    0.091 (0.036 to 0.147)
    0.093 (0.041 to 0.146)
    -0.011 (-0.070 to 0.048)
    0.107 (0.052 to 0.161)
        Week 4 (n=98, 103, 103, 104, 127, 84, 110)
    -0.002 (-0.063 to 0.059)
    0.039 (-0.021 to 0.099)
    0.078 (0.018 to 0.138)
    0.086 (0.027 to 0.146)
    0.094 (0.037 to 0.151)
    -0.020 (-0.085 to 0.045)
    0.145 (0.086 to 0.204)
        Week 8 (n=90, 96, 100, 96, 125, 76, 105)
    0.019 (-0.044 to 0.082)
    0.007 (-0.055 to 0.069)
    0.071 (0.010 to 0.133)
    0.102 (0.040 to 0.163)
    0.141 (0.083 to 0.199)
    0.002 (-0.066 to 0.069)
    0.124 (0.064 to 0.184)
        Treatment Period Avg(n=108,109,108,109,132,95,110)
    0.005 (-0.049 to 0.059)
    0.006 (-0.047 to 0.059)
    0.069 (0.016 to 0.123)
    0.094 (0.041 to 0.148)
    0.108 (0.057 to 0.159)
    -0.002 (-0.059 to 0.056)
    0.127 (0.075 to 0.180)
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.463
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.029
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.048
         upper limit
    0.105
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.576
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.022
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.055
         upper limit
    0.098
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.047
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.078
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.001
         upper limit
    0.154
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.009
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.102
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.025
         upper limit
    0.179
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    227
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.104
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.031
         upper limit
    0.178
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.003
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.118
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.041
         upper limit
    0.194
    Notes
    [2] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.685
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.018
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.068
         upper limit
    0.103
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.176
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.059
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.026
         upper limit
    0.144
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.024
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.098
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.013
         upper limit
    0.183
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.106
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.021
         upper limit
    0.191
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    227
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.114
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.032
         upper limit
    0.196
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.165
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.081
         upper limit
    0.249
    Notes
    [3] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.707
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.017
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.072
         upper limit
    0.106
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.904
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.005
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.083
         upper limit
    0.094
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.121
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.018
         upper limit
    0.157
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.026
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.012
         upper limit
    0.188
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    227
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.139
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.055
         upper limit
    0.224
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    = 0.006
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.122
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.035
         upper limit
    0.209
    Notes
    [4] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.856
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.007
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.068
         upper limit
    0.081
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.832
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.008
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.066
         upper limit
    0.082
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.06
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.071
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.003
         upper limit
    0.145
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.096
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.022
         upper limit
    0.17
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    227
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.039
         upper limit
    0.181
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.129
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.055
         upper limit
    0.202
    Notes
    [5] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in Fractional exhaled nitic oxide (FENO) at Weeks 2, 4, 8, 12 and average over the Treatment Period

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    End point title
    Change from baseline in Fractional exhaled nitic oxide (FENO) at Weeks 2, 4, 8, 12 and average over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the last value obtained prior to the first dose of investigational product. Analyses were based on a MMRM with change from baseline on the log-scale as the response, treatment, visit, treatment by visit interaction and region as fixed effects, and log-transformed baseline value and baseline by visit interaction as covariates. The reported number of subjects analysed corresponds to Week 2 and for Weeks 4, 8, 12 and average over the Treatment Period, the number of subjects analysed are provided as comment in the row titles.
    End point type
    Secondary
    End point timeframe
    At Baseline and Weeks 2, 4, 8, and 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    107
    105
    107
    102
    127
    95
    104
    Units: ppb
    geometric mean (confidence interval 95%)
        Week 2
    1.307 (1.190 to 1.436)
    1.223 (1.113 to 1.343)
    1.175 (1.070 to 1.290)
    1.152 (1.048 to 1.267)
    0.959 (0.876 to 1.049)
    1.396 (1.263 to 1.542)
    0.880 (0.801 to 0.967)
        Week 4 (n=95,100,103,102,126,84,105)
    1.229 (1.109 to 1.363)
    1.203 (1.087 to 1.332)
    1.220 (1.103 to 1.349)
    1.118 (1.011 to 1.237)
    0.980 (0.891 to 1.078)
    1.321 (1.184 to 1.475)
    0.928 (0.840 to 1.025)
        Week 8 (n=87,90,97,93,122,76,101)
    1.294 (1.157 to 1.447)
    1.316 (1.179 to 1.470)
    1.250 (1.122 to 1.392)
    1.206 (1.082 to 1.345)
    1.021 (0.923 to 1.129)
    1.411 (1.252 to 1.591)
    0.906 (0.815 to 1.007)
        Week 12 (n=79,89,89,88,121,70,100)
    1.367 (1.219 to 1.532)
    1.405 (1.258 to 1.569)
    1.281 (1.148 to 1.431)
    1.198 (1.072 to 1.337)
    0.958 (0.866 to 1.060)
    1.474 (1.305 to 1.664)
    0.918 (0.826 to 1.022)
        Treatment Period Avg(n=109,107,108,109,132,95,110)
    1.298 (1.188 to 1.419)
    1.284 (1.176 to 1.402)
    1.231 (1.128 to 1.343)
    1.168 (1.070 to 1.275)
    0.979 (0.901 to 1.064)
    1.399 (1.273 to 1.538)
    0.908 (0.833 to 0.989)
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.322
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.936
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.822
         upper limit
    1.067
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.047
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.876
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.768
         upper limit
    0.999
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.01
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.842
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.739
         upper limit
    0.959
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.825
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.724
         upper limit
    0.941
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.687
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.606
         upper limit
    0.779
    Statistical analysis title
    Statistical Analysis at Week 2
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority [6]
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.63
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.553
         upper limit
    0.719
    Notes
    [6] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.329
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.931
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.805
         upper limit
    1.076
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.203
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.911
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.789
         upper limit
    1.052
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.273
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.923
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8
         upper limit
    1.065
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.023
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.846
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.734
         upper limit
    0.977
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.742
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.646
         upper limit
    0.852
    Statistical analysis title
    Statistical Analysis at Week 4
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority [7]
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.703
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.609
         upper limit
    0.81
    Notes
    [7] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.283
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.917
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.783
         upper limit
    1.074
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.386
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.933
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.797
         upper limit
    1.092
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.126
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.886
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.758
         upper limit
    1.035
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.05
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.855
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.731
         upper limit
    1
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.723
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.623
         upper limit
    0.84
    Statistical analysis title
    Statistical Analysis at Week 8
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority [8]
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.642
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    0.749
    Notes
    [8] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.359
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.927
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.789
         upper limit
    1.09
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    Placebo to AZD7594 v AZD7594 90 μg
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.556
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.953
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.813
         upper limit
    1.118
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.084
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.869
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.742
         upper limit
    1.019
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.813
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.693
         upper limit
    0.953
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.559
         upper limit
    0.757
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority [9]
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.623
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.533
         upper limit
    0.729
    Notes
    [9] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.231
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.928
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.821
         upper limit
    1.049
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.17
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.918
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.812
         upper limit
    1.037
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.039
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.879
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.778
         upper limit
    0.994
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.835
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.739
         upper limit
    0.943
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.622
         upper limit
    0.787
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority [10]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.649
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.575
         upper limit
    0.732
    Notes
    [10] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in trough Forced vital capacity (FVC) at Week 12 and average over the Treatment Period

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    End point title
    Change from baseline in trough Forced vital capacity (FVC) at Week 12 and average over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS(Full Analysis Set).Trough value was defined as the mean of the 2 measurements 30 minutes apart(23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Week 2 to Week 12).Baseline was defined as the mean of the 2 measured values before first IP administration(30 minutes apart, at −45 minutes and −15 minutes, before IP administration) on Day 1. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. Analysis of covariance with treatment and region as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. Reported number of subjects analysed corresponds to Week 12 and for average over the Treatment Period, the number of subjects analysed are provided as comment in row title.
    End point type
    Secondary
    End point timeframe
    At Baseline and Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    83
    90
    92
    90
    123
    70
    103
    Units: Liters
    least squares mean (confidence interval 95%)
        Week 12
    0.027 (-0.047 to 0.101)
    -0.017 (-0.089 to 0.056)
    0.076 (0.005 to 0.148)
    0.119 (0.047 to 0.191)
    0.088 (0.021 to 0.155)
    0.061 (-0.018 to 0.141)
    0.118 (0.048 to 0.188)
        Treatment Period Avg(n=108,109,108,109,132,95,110)
    0.044 (-0.017 to 0.106)
    0.019 (-0.041 to 0.080)
    0.087 (0.026 to 0.148)
    0.127 (0.066 to 0.188)
    0.091 (0.033 to 0.149)
    0.046 (-0.020 to 0.112)
    0.121 (0.062 to 0.181)
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.519
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.034
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.139
         upper limit
    0.07
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.141
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.078
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.181
         upper limit
    0.026
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.772
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.015
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.088
         upper limit
    0.119
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.27
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.058
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.045
         upper limit
    0.162
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    193
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.592
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.027
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.072
         upper limit
    0.126
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    superiority [11]
    P-value
    = 0.275
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.057
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.045
         upper limit
    0.158
    Notes
    [11] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.963
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.002
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.087
         upper limit
    0.083
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.533
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.027
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.112
         upper limit
    0.058
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.342
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.041
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.044
         upper limit
    0.126
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.061
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.081
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.004
         upper limit
    0.165
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    193
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.278
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.045
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.037
         upper limit
    0.127
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    superiority [12]
    P-value
    = 0.079
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.075
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.009
         upper limit
    0.159
    Notes
    [12] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and average over the Treatment Period

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    End point title
    Change from baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and average over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the ACQ-5 score at Visit 3. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. Analysis of covariance with treatment and region as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. The questionnaire has 5 items; each item is scored on a scale of 0 to 6, where higher scores represent more severe impairment/symptoms. The overall ACQ-5 score is the average of the scores for each of the questions included in the questionnaire. Reported number of subjects analysed corresponds to Week 12 and for average over the Treatment Period, the number of subjects analysed are provided as comment in row title.
    End point type
    Secondary
    End point timeframe
    At Baseline and Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    83
    91
    93
    90
    122
    70
    103
    Units: units on a scale
    least squares mean (confidence interval 95%)
        Week 12
    -0.289 (-0.412 to -0.166)
    -0.394 (-0.513 to -0.274)
    -0.357 (-0.476 to -0.239)
    -0.330 (-0.449 to -0.210)
    -0.406 (-0.514 to -0.297)
    -0.137 (-0.269 to -0.004)
    -0.360 (-0.474 to -0.245)
        Treatment Period Avg(n=108,110,108,110,132,101,110
    -0.215 (-0.307 to -0.122)
    -0.230 (-0.322 to -0.139)
    -0.220 (-0.311 to -0.128)
    -0.291 (-0.382 to -0.199)
    -0.306 (-0.394 to -0.219)
    -0.090 (-0.187 to 0.008)
    -0.269 (-0.359 to -0.179)
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.088
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.153
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.328
         upper limit
    0.023
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.257
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.43
         upper limit
    -0.084
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    163
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.221
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.393
         upper limit
    -0.049
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.029
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.193
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.366
         upper limit
    -0.02
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.269
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.434
         upper limit
    -0.104
    Statistical analysis title
    Statistical Analysis at Week 12
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    superiority [13]
    P-value
    = 0.01
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.223
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.393
         upper limit
    -0.054
    Notes
    [13] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.055
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.125
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.253
         upper limit
    0.003
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.029
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.141
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.268
         upper limit
    -0.014
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    163
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.044
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.257
         upper limit
    -0.003
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.201
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.328
         upper limit
    -0.074
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.217
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.339
         upper limit
    -0.094
    Statistical analysis title
    Statistical Analysis for Treatment period average
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    superiority [14]
    P-value
    = 0.005
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.179
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.305
         upper limit
    -0.053
    Notes
    [14] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in average morning Peak Expiratory Flow (PEF) over the Treatment Period

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    End point title
    Change from baseline in average morning Peak Expiratory Flow (PEF) over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    89
    94
    97
    92
    122
    73
    104
    Units: Liters/minute
        least squares mean (confidence interval 95%)
    -4.036 (-10.518 to 2.447)
    -5.718 (-11.994 to 0.557)
    -2.576 (-8.768 to 3.617)
    3.745 (-2.558 to 10.048)
    4.900 (-1.010 to 10.810)
    -11.699 (-18.749 to -4.649)
    -1.208 (-7.209 to 4.793)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.097
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    7.664
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.403
         upper limit
    16.73
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.19
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    5.981
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.98
         upper limit
    14.941
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.045
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    9.123
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.195
         upper limit
    18.052
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    15.444
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.443
         upper limit
    24.445
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    16.599
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.031
         upper limit
    25.167
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    177
    Analysis specification
    Pre-specified
    Analysis type
    superiority [15]
    P-value
    = 0.019
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.491
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.726
         upper limit
    19.256
    Notes
    [15] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in average evening PEF over the Treatment Period

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    End point title
    Change from baseline in average evening PEF over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    88
    93
    96
    92
    119
    73
    102
    Units: Liters/minute
        least squares mean (confidence interval 95%)
    -5.418 (-11.792 to 0.955)
    -5.654 (-11.843 to 0.534)
    -3.983 (-10.081 to 2.114)
    2.441 (-3.738 to 8.620)
    4.178 (-1.642 to 9.997)
    -7.816 (-14.712 to -0.921)
    -1.687 (-7.602 to 4.227)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.597
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.398
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.494
         upper limit
    11.29
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    166
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.629
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.162
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.623
         upper limit
    10.948
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.389
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    3.833
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.907
         upper limit
    12.573
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.022
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.258
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.456
         upper limit
    19.059
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    11.994
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.571
         upper limit
    20.417
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    superiority [16]
    P-value
    = 0.163
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    6.129
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.479
         upper limit
    14.737
    Notes
    [16] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in average daily use of rescue medication over the Treatment Period

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    End point title
    Change from baseline in average daily use of rescue medication over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    86
    86
    91
    79
    109
    66
    93
    Units: number of puffs
        least squares mean (confidence interval 95%)
    -0.370 (-0.502 to -0.237)
    -0.282 (-0.415 to -0.149)
    -0.226 (-0.356 to -0.096)
    -0.435 (-0.572 to -0.297)
    -0.435 (-0.560 to -0.310)
    -0.127 (-0.276 to 0.023)
    -0.304 (-0.432 to -0.175)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.243
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.431
         upper limit
    -0.054
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.108
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.155
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.344
         upper limit
    0.034
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    157
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.295
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.099
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.286
         upper limit
    0.087
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.308
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    -0.116
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.308
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.489
         upper limit
    -0.126
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    superiority [17]
    P-value
    = 0.062
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.177
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.362
         upper limit
    0.009
    Notes
    [17] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in percent night-time awakening days over the Treatment Period

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    End point title
    Change from baseline in percent night-time awakening days over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    89
    94
    97
    92
    122
    73
    104
    Units: percentage
        least squares mean (confidence interval 95%)
    -14.281 (-18.408 to -10.154)
    -12.260 (-16.263 to -8.257)
    -8.649 (-12.579 to -4.718)
    -12.085 (-16.102 to -8.068)
    -13.017 (-16.790 to -9.244)
    -4.288 (-8.814 to 0.238)
    -15.910 (-19.753 to -12.067)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -9.993
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.795
         upper limit
    -4.191
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.972
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.694
         upper limit
    -2.251
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.133
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -4.361
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.051
         upper limit
    1.329
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.008
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.797
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.555
         upper limit
    -2.04
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -8.729
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.195
         upper limit
    -3.264
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    177
    Analysis specification
    Pre-specified
    Analysis type
    superiority [18]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -11.622
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.211
         upper limit
    -6.034
    Notes
    [18] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in average daily asthma symptom score over the Treatment Period

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    End point title
    Change from baseline in average daily asthma symptom score over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. During the Run-in and Treatment Periods, subjects recorded the severity of their asthma symptoms during night-time and day-time each morning and evening, using the eDiary. Asthma symptom scores during night-time/day-time were assessed by the subject each morning/evening according to the following scoring system and recorded on the eDiary: 0: No asthma symptoms, 1: The subjects were aware of their asthma symptoms but they can easily tolerate the symptoms, 2: asthma was causing enough discomfort to cause problems with sleep, 3: Subjects were unable to sleep/do normal activities because of their asthma.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    86
    86
    91
    79
    109
    66
    93
    Units: Unit on a scale
        least squares mean (confidence interval 95%)
    -0.303 (-0.385 to -0.220)
    -0.201 (-0.283 to -0.118)
    -0.229 (-0.310 to -0.149)
    -0.321 (-0.407 to -0.235)
    -0.275 (-0.353 to -0.198)
    -0.091 (-0.184 to 0.003)
    -0.296 (-0.376 to -0.216)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.212
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.329
         upper limit
    -0.094
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.066
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.228
         upper limit
    0.007
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    157
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.02
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.139
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.255
         upper limit
    -0.022
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.35
         upper limit
    -0.11
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.185
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.298
         upper limit
    -0.071
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    superiority [19]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.206
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.321
         upper limit
    -0.09
    Notes
    [19] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in percent asthma control days over the Treatment Period

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    End point title
    Change from baseline in percent asthma control days over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Asthma-control days was defined as days with no symptoms, no night-waking, no use of rescue medication. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    86
    86
    91
    79
    109
    66
    93
    Units: percent
        least squares mean (confidence interval 95%)
    15.470 (9.547 to 21.394)
    11.362 (5.435 to 17.290)
    12.646 (6.865 to 18.427)
    15.925 (9.775 to 22.076)
    14.479 (8.896 to 20.062)
    5.859 (-0.813 to 12.532)
    13.037 (7.301 to 18.772)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.026
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    9.611
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.18
         upper limit
    18.042
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    5.503
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.927
         upper limit
    13.933
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    157
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.11
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    6.787
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.546
         upper limit
    15.119
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.022
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.066
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.461
         upper limit
    18.672
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.038
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    8.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.489
         upper limit
    16.75
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    superiority [20]
    P-value
    = 0.09
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    7.178
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.112
         upper limit
    15.467
    Notes
    [20] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in percent rescue-free days over the Treatment Period

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    End point title
    Change from baseline in percent rescue-free days over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). A rescue-free day (RFD) was defined as a day with no use of rescue medication. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    86
    86
    91
    79
    109
    66
    93
    Units: percent
        least squares mean (confidence interval 95%)
    31.138 (24.019 to 38.257)
    24.178 (17.045 to 31.312)
    21.960 (14.940 to 28.980)
    34.991 (27.549 to 42.433)
    30.775 (24.025 to 37.526)
    23.202 (15.188 to 31.215)
    28.260 (21.308 to 35.211)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.123
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    7.936
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.16
         upper limit
    18.031
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.849
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.977
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.112
         upper limit
    11.065
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    157
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.807
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.242
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.233
         upper limit
    8.748
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.025
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    11.789
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.488
         upper limit
    22.09
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.127
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    7.574
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.16
         upper limit
    17.307
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    superiority [21]
    P-value
    = 0.318
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    5.058
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.874
         upper limit
    14.99
    Notes
    [21] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Change from baseline in percent symptom-free days over the Treatment Period

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    End point title
    Change from baseline in percent symptom-free days over the Treatment Period
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Days without asthma symptoms, or symptom-free days, were defined as days without asthma symptoms, short-acting β-agonist (SABA) use, systemic corticosteroid use, or need for urgent asthma care.
    End point type
    Secondary
    End point timeframe
    Week 0 (7 days prior to randomisation) to Week 12
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    86
    86
    91
    79
    109
    66
    93
    Units: percent
        least squares mean (confidence interval 95%)
    13.780 (7.873 to 19.686)
    10.521 (4.608 to 16.435)
    11.935 (6.169 to 17.701)
    14.673 (8.539 to 20.806)
    13.451 (7.883 to 19.018)
    3.329 (-3.319 to 9.977)
    14.018 (8.293 to 19.743)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.015
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.046
         upper limit
    18.855
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.093
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    7.192
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.208
         upper limit
    15.592
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    157
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.042
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    8.606
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.298
         upper limit
    16.913
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.01
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    11.344
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.773
         upper limit
    19.914
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.122
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.021
         upper limit
    18.222
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    superiority [22]
    P-value
    = 0.011
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.689
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.424
         upper limit
    18.953
    Notes
    [22] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Time to recurrent Composite endpoint for severe exacerbations of asthma (CompEx) event

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    End point title
    Time to recurrent Composite endpoint for severe exacerbations of asthma (CompEx) event
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). CompEx is a composite endpoint combining severe exacerbations of asthma and diary events. CompEx is a composite surrogate endpoint for severe exacerbations of asthma, recently developed by AstraZeneca (it is not yet a regulatory-approved clinical endpoint). Severe exacerbations are defined as those episodes that lead to hospitalisation, emergency room visit and/or treatment with oral corticosteroids. Time at risk was calculated as [(date of last treatment – date of randomisation)+1 – recovery time. Recovery time was the sum (from i=1 to k) of (min with event end date +7, date of last treatment] – with event start date +1). No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    From Screening (Within 21-28 days before randomisation) to Week 12/End of treatment or Early Termination Visit
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    110
    112
    111
    113
    134
    113
    112
    Units: Years
        number (not applicable)
    21.3
    22.2
    22.6
    23.1
    29.0
    18.6
    24.4
    No statistical analyses for this end point

    Secondary: Annualized CompEx event rate

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    End point title
    Annualized CompEx event rate
    End point description
    To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). CompEx is a composite endpoint combining severe exacerbations of asthma and diary events. CompEx is a composite surrogate endpoint for severe exacerbations of asthma, recently developed by AstraZeneca (it is not yet a regulatory-approved clinical endpoint). Severe exacerbations are defined as those episodes that lead to hospitalisation, emergency room visit and/or treatment with oral corticosteroids. CompEx Model: Rates, rate ratios, and p-values were from a negative binomial model analysis, with event count as the dependent variable, with treatment and region as covariates and log-transformed time at risk (days) as an offset variable to account for overdispersion.
    End point type
    Secondary
    End point timeframe
    From Screening (Within 21-28 days before randomisation) to Week 12/End of treatment or Early Termination Visit
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    110
    112
    111
    113
    134
    113
    112
    Units: Annual rate
        number (not applicable)
    2.06
    2.20
    2.04
    0.67
    0.50
    4.71
    0.75
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    223
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.035
    Method
    Negative Binominal Model
    Parameter type
    Estimate
    Point estimate
    0.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.2
         upper limit
    0.94
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    225
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.05
    Method
    Negative Binominal Model
    Parameter type
    Estimate
    Point estimate
    0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.22
         upper limit
    1
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    224
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.032
    Method
    Negative Binominal Model
    Parameter type
    Estimate
    Point estimate
    0.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.2
         upper limit
    0.93
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    226
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Negative Binominal Model
    Parameter type
    Estimate
    Point estimate
    0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.06
         upper limit
    0.34
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    247
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Negative Binominal Model
    Parameter type
    Estimate
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.04
         upper limit
    0.25
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    225
    Analysis specification
    Pre-specified
    Analysis type
    superiority [23]
    P-value
    < 0.001
    Method
    Negative Binominal Model
    Parameter type
    Estimate
    Point estimate
    0.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.07
         upper limit
    0.37
    Notes
    [23] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Observed maximum concentration at steady state (Css,max) of AZD7594 at Day 84

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    End point title
    Observed maximum concentration at steady state (Css,max) of AZD7594 at Day 84
    End point description
    To describe the (steady state) pharmacokinetic (PK) of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 hour (h) post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    17
    14
    15
    16
    27
    0 [24]
    0 [25]
    Units: pmol/L
        geometric mean (geometric coefficient of variation)
    48.45 ± 68.65
    114.90 ± 99.12
    69.71 ± 105.94
    154.50 ± 144.67
    200.00 ± 113.05
    ±
    ±
    Notes
    [24] - Subjects from this arm were excluded from the PK analysis set.
    [25] - Subjects from this arm were excluded from the PK analysis set.
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Assessment of Dose Proportionality of AZD7594 PK Parameter at Visit 7 (Day 84) (PK Analysis Set)
    Comparison groups
    AZD7594 50 μg v AZD7594 90 μg v AZD7594 180 μg v AZD7594 360 μg v AZD7594 720 μg
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Slope
    Point estimate
    0.476
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.321
         upper limit
    0.632
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.094

    Secondary: Observed minimum concentration at the end of the dosing interval (Css,min) of AZD7594 at Day 84

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    End point title
    Observed minimum concentration at the end of the dosing interval (Css,min) of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    3
    10
    11
    13
    26
    0 [26]
    0 [27]
    Units: pmol/L
        geometric mean (geometric coefficient of variation)
    14.41 ± 37.59
    21.45 ± 43.12
    30.22 ± 43.28
    70.58 ± 46.22
    85.13 ± 108.41
    ±
    ±
    Notes
    [26] - Subjects from this arm were excluded from the PK analysis set.
    [27] - Subjects from this arm were excluded from the PK analysis set.
    No statistical analyses for this end point

    Secondary: Time to maximum concentration at steady state, taken directly from the individual concentration-time curve (tss, max) of AZD7594 at Day 84

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    End point title
    Time to maximum concentration at steady state, taken directly from the individual concentration-time curve (tss, max) of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    17
    14
    15
    16
    27
    0 [28]
    0 [29]
    Units: hours
        median (full range (min-max))
    0.25 (0.23 to 2.17)
    0.25 (0.00 to 0.98)
    0.25 (0.20 to 2.00)
    0.25 (0.00 to 2.00)
    0.25 (0.00 to 23.98)
    ( to )
    ( to )
    Notes
    [28] - Subjects from this arm were excluded from the PK analysis set.
    [29] - Subjects from this arm were excluded from the PK analysis set.
    No statistical analyses for this end point

    Secondary: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD7594 at Day 84

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    End point title
    Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    15
    14
    14
    16
    26
    0 [30]
    0 [31]
    Units: h*pmol/L
        geometric mean (geometric coefficient of variation)
    167.50 ± 123.50
    573.00 ± 116.00
    719.10 ± 134.58
    1435.00 ± 140.28
    2622.00 ± 98.88
    ±
    ±
    Notes
    [30] - Subjects from this arm were excluded from the PK analysis set.
    [31] - Subjects from this arm were excluded from the PK analysis set.
    No statistical analyses for this end point

    Secondary: Area under the plasma concentration-curve within a dosing interval (AUCτ) of AZD7594 at Day 84

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    End point title
    Area under the plasma concentration-curve within a dosing interval (AUCτ) of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    3
    10
    11
    13
    26
    0 [32]
    0 [33]
    Units: h*pmol/L
        geometric mean (geometric coefficient of variation)
    530.50 ± 32.57
    928.60 ± 37.52
    1137.00 ± 52.06
    2205.00 ± 52.32
    2622.00 ± 98.88
    ±
    ±
    Notes
    [32] - Subjects from this arm were excluded from the PK analysis set.
    [33] - Subjects from this arm were excluded from the PK analysis set.
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Assessment of Dose Proportionality of AZD7594 PK Parameter at Visit 7 (Day 84) (PK Analysis Set)
    Comparison groups
    AZD7594 50 μg v AZD7594 90 μg v AZD7594 180 μg v AZD7594 360 μg v AZD7594 720 μg
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Slope
    Point estimate
    0.555
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.402
         upper limit
    0.709
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.092

    Secondary: Average plasma concentration during a dosing interval at steady state (Css,avg) of AZD7594 at Day 84

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    End point title
    Average plasma concentration during a dosing interval at steady state (Css,avg) of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    3
    10
    11
    13
    26
    0 [34]
    0 [35]
    Units: pmol/L
        geometric mean (geometric coefficient of variation)
    22.10 ± 32.57
    38.69 ± 37.52
    47.37 ± 52.06
    91.86 ± 52.32
    109.30 ± 98.88
    ±
    ±
    Notes
    [34] - Subjects from this arm were excluded from the PK analysis set.
    [35] - Subjects from this arm were excluded from the PK analysis set.
    No statistical analyses for this end point

    Secondary: Dose normalised Css,max (Css,max/D) of AZD7594 at Day 84

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    End point title
    Dose normalised Css,max (Css,max/D) of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    17
    14
    15
    16
    27
    0 [36]
    0 [37]
    Units: pmol/L/umol
        geometric mean (geometric coefficient of variation)
    587.80 ± 68.65
    774.40 ± 99.12
    234.90 ± 105.94
    260.40 ± 144.67
    168.50 ± 113.05
    ±
    ±
    Notes
    [36] - Subjects from this arm were excluded from the PK analysis set.
    [37] - Subjects from this arm were excluded from the PK analysis set.
    No statistical analyses for this end point

    Secondary: Dose normalised AUCτ (AUCτ/D) of AZD7594 at Day 84

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    End point title
    Dose normalised AUCτ (AUCτ/D) of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    3
    10
    11
    13
    26
    0 [38]
    0 [39]
    Units: h*pmol/μmol
        geometric mean (geometric coefficient of variation)
    6436.00 ± 32.57
    6259.00 ± 37.52
    3831.00 ± 52.06
    3715.00 ± 52.32
    2209.00 ± 98.88
    ±
    ±
    Notes
    [38] - Subjects from this arm were excluded from the PK analysis set.
    [39] - Subjects from this arm were excluded from the PK analysis set.
    No statistical analyses for this end point

    Secondary: Percentage Fluctuation index within a dosing interval of AZD7594 at Day 84

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    End point title
    Percentage Fluctuation index within a dosing interval of AZD7594 at Day 84
    End point description
    To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    3
    10
    11
    13
    26
    0 [40]
    0 [41]
    Units: percentage
        geometric mean (geometric coefficient of variation)
    387.80 ± 21.97
    326.60 ± 37.40
    148.90 ± 38.27
    172.10 ± 44.32
    98.22 ± 61.36
    ±
    ±
    Notes
    [40] - Subjects from this arm were excluded from the PK analysis set.
    [41] - Subjects from this arm were excluded from the PK analysis set.
    No statistical analyses for this end point

    Secondary: Change from baseline of area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC0-24), compared to Placebo of AZD7594 at Day 84

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    End point title
    Change from baseline of area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC0-24), compared to Placebo of AZD7594 at Day 84
    End point description
    To describe the pharmacodynamics of AZD7594 by measuring cortisol suppression in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (Pharmacodynamic Analysis Set). Baseline was defined as the Day -1 value. Analyses were based on an ANCOVA model with change from baseline on the log-scale as the response, treatment as a fixed effect, and log-transformed baseline value as a covariate.
    End point type
    Secondary
    End point timeframe
    Day 84 (at 0 [pre-dose], 2, 4, 6, 8, 10, 12, 16, 20, 22 and 24 hours relative to IP administration)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    19
    16
    16
    17
    27
    14
    17
    Units: ng/mL
        geometric mean (confidence interval 95%)
    1.029 (0.920 to 1.152)
    1.140 (1.009 to 1.287)
    1.151 (1.018 to 1.300)
    1.003 (0.891 to 1.129)
    0.934 (0.850 to 1.026)
    1.019 (0.895 to 1.161)
    1.011 (0.898 to 1.137)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    AZD7594 50 μg v Placebo to AZD7594
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.909
    Method
    ANCOVA
    Parameter type
    geometric LSMean ratio
    Point estimate
    1.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.851
         upper limit
    1.199
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    AZD7594 90 μg v Placebo to AZD7594
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.218
    Method
    ANCOVA
    Parameter type
    geometric LSMean ratio
    Point estimate
    1.118
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.935
         upper limit
    1.336
    Statistical analysis title
    Statistical Analysis 3
    Comparison groups
    AZD7594 180 μg v Placebo to AZD7594
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.181
    Method
    ANCOVA
    Parameter type
    geometric LSMean ratio
    Point estimate
    1.129
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.944
         upper limit
    1.349
    Statistical analysis title
    Statistical Analysis 4
    Comparison groups
    AZD7594 360 μg v Placebo to AZD7594
    Number of subjects included in analysis
    31
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.859
    Method
    ANCOVA
    Parameter type
    geometric LSMean ratio
    Point estimate
    0.984
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.825
         upper limit
    1.174
    Statistical analysis title
    Statistical Analysis 5
    Comparison groups
    AZD7594 720 μg v Placebo to AZD7594
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.285
    Method
    ANCOVA
    Parameter type
    geometric LSMean ratio
    Point estimate
    0.916
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.78
         upper limit
    1.077
    Statistical analysis title
    Statistical Analysis 6
    Comparison groups
    Placebo to AZD7594 v Fluticasone furoate
    Number of subjects included in analysis
    31
    Analysis specification
    Pre-specified
    Analysis type
    superiority [42]
    P-value
    = 0.923
    Method
    ANCOVA
    Parameter type
    geometric LSMean ratio
    Point estimate
    0.991
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.831
         upper limit
    1.182
    Notes
    [42] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

    Secondary: Number of subjects with adverse events

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    End point title
    Number of subjects with adverse events
    End point description
    To evaluate the safety and tolerability of AZD7594 in relation to Placebo in asthmatics symptomatic on low dose ICS (Safety Analysis Set). No statistical analysis is done for this endpoint.
    End point type
    Secondary
    End point timeframe
    From screening to follow-up period (7 to 10 days after visit 7)
    End point values
    AZD7594 50 μg AZD7594 90 μg AZD7594 180 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Number of subjects analysed
    110
    112
    111
    113
    134
    113
    112
    Units: Subjects
        Any AE
    35
    45
    39
    54
    46
    47
    34
        death
    0
    0
    0
    1
    0
    0
    0
        Any SAE
    0
    3
    1
    3
    3
    0
    1
        Any AE leading to discontinuation of IP
    6
    8
    4
    11
    4
    20
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Screening to follow-up period (7to 10 days after visit 7)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    AZD7594 50 μg
    Reporting group description
    Oral inhalation of AZD5794 55 microgram/ 50 microgram (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 180 μg
    Reporting group description
    Oral inhalation of AZD5794 198 microgram/ 180 microgram (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 90 μg
    Reporting group description
    Oral inhalation of AZD5794 99 microgram/ 90 microgram (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 360 μg
    Reporting group description
    Oral inhalation of AZD5794 396 microgram/ 360 microgram (nominal dose/delivered dose) once daily.

    Reporting group title
    AZD7594 720 μg
    Reporting group description
    Oral inhalation of AZD5794 792 microgram/ 720 microgram (nominal dose/delivered dose) once daily.

    Reporting group title
    Placebo to AZD7594
    Reporting group description
    Oral inhalation of placebo to AZD7594 once daily.

    Reporting group title
    Fluticasone furoate
    Reporting group description
    Oral inhalation of fluticasone furoate 100 microgram once daily.

    Serious adverse events
    AZD7594 50 μg AZD7594 180 μg AZD7594 90 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 110 (0.00%)
    1 / 111 (0.90%)
    3 / 112 (2.68%)
    3 / 113 (2.65%)
    3 / 134 (2.24%)
    0 / 113 (0.00%)
    1 / 112 (0.89%)
         number of deaths (all causes)
    0
    0
    0
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 112 (0.00%)
    0 / 113 (0.00%)
    1 / 134 (0.75%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 112 (0.00%)
    0 / 113 (0.00%)
    1 / 134 (0.75%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 112 (0.00%)
    0 / 113 (0.00%)
    1 / 134 (0.75%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 112 (0.00%)
    0 / 113 (0.00%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 112 (0.00%)
    1 / 113 (0.88%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 112 (0.00%)
    1 / 113 (0.88%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 110 (0.00%)
    1 / 111 (0.90%)
    1 / 112 (0.89%)
    1 / 113 (0.88%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    1 / 112 (0.89%)
    0 / 113 (0.00%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    1 / 112 (0.89%)
    0 / 113 (0.00%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    1 / 112 (0.89%)
    0 / 113 (0.00%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    1 / 112 (0.89%)
    0 / 113 (0.00%)
    0 / 134 (0.00%)
    0 / 113 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    AZD7594 50 μg AZD7594 180 μg AZD7594 90 μg AZD7594 360 μg AZD7594 720 μg Placebo to AZD7594 Fluticasone furoate
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 110 (12.73%)
    8 / 111 (7.21%)
    15 / 112 (13.39%)
    14 / 113 (12.39%)
    8 / 134 (5.97%)
    24 / 113 (21.24%)
    11 / 112 (9.82%)
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    7 / 110 (6.36%)
    2 / 111 (1.80%)
    6 / 112 (5.36%)
    10 / 113 (8.85%)
    3 / 134 (2.24%)
    19 / 113 (16.81%)
    3 / 112 (2.68%)
         occurrences all number
    7
    2
    6
    10
    3
    20
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 110 (6.36%)
    6 / 111 (5.41%)
    9 / 112 (8.04%)
    4 / 113 (3.54%)
    5 / 134 (3.73%)
    6 / 113 (5.31%)
    9 / 112 (8.04%)
         occurrences all number
    7
    6
    9
    4
    6
    6
    9

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Apr 2019
    Deletion of peak FEV1 from the secondary efficacy endpoints. Update of the inclusion criteria to include only subjects with BMI ≤ 35. Deletion of the expected number of subjects in the US vs. non-US sites. Removal of interim futility analysis. Specification of inclusion criterion #7 (pre-bronchodilator FEV1 at Visit 3 between 40% and 90% predicted). Deletion of QT interval corrected using Bazett’s formula; addition of appropriate electrocardiogram parameters. Clarification of exclusion criterion #3 and exclusion criterion #21 for alcohol and drug abuse. Clarified the required treatments for postmenopausal subjects. Clarified that the subjects were discontinued when specified criteria are met. Deletion of measure peak expiratory flow at Screening. Clarification of the number of measurement and timing of spirometry. Clarification of the compliance rate in the Run-in Period and the expected compliance rate in the Treatment Period. Clarification that peak expiratory flow was measured at home after completing the morning and evening diary. Clarification that Forced oscillation technique evaluation and training took place at Visit 1, instead of Visit 2. Deletion of the description that rescue medication should be recorded as concomitant medication. Clarification that the analysis set used for demographic and baseline characteristics was Full analysis set. Clarification that baseline asthma severity was assessed using the pre-SABA value at Visit 2, instead of pre-bronchodilator value at Visit 1. The number of subjects who met the reversibility criteria was deleted. “Individual plasma concentrations vs. time on Week 12 (Day 84) plotted on linear and semi-logarithmic scale with all treatments overlaid on the same plot and separate plots for each subject” was no longer provided as part of PK analysis. Geometric SD was no longer presented on figures of geometric mean for concentration-time data as part of the PK analysis. Clarification of the definition of ACQ-5 responder.

    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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