Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A randomized, double-blind, double-dummy, parallel group, multicenter study of once daily Fluticasone Furoate/Vilanterol 100/25 mcg Inhalation Powder, twice daily Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and twice daily Fluticasone Propionate 250 mcg Inhalation Powder in the treatment of persistent asthma in adults and adolescents already adequately controlled on twice-daily inhaled corticosteroid and long-acting beta2 agonist.

    Summary
    EudraCT number
    		 2014-002253-19
    Trial protocol
    		 ES   NL   CZ   DE  
    Global end of trial date
    25 Nov 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 May 2017
    First version publication date
    24 May 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    201378
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    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
    14 Mar 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Nov 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to demonstrate non-inferiority of RELVAR ELLIPTA 100/25 once-daily to SERETIDE ACCUHALER/DISKUS 250/50 twice-daily in adult and adolescent subjects 12 years of age and older with persistent bronchial asthma, adequately controlled on twice-daily ICS/LABA.
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Mar 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Russian Federation: 597
    Country: Number of subjects enrolled
    United States: 491
    Country: Number of subjects enrolled
    Argentina: 439
    Country: Number of subjects enrolled
    Germany: 425
    Country: Number of subjects enrolled
    Mexico: 326
    Country: Number of subjects enrolled
    Romania: 306
    Country: Number of subjects enrolled
    Czech Republic: 151
    Country: Number of subjects enrolled
    Chile: 109
    Country: Number of subjects enrolled
    Spain: 100
    Country: Number of subjects enrolled
    Netherlands: 98
    Country: Number of subjects enrolled
    Brazil: 71
    Country: Number of subjects enrolled
    Korea, Republic of: 49
    Worldwide total number of subjects
    3162
    EEA total number of subjects
    1080
    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)
    7
    Adolescents (12-17 years)
    167
    Adults (18-64 years)
    2620
    From 65 to 84 years
    368
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Eligible participants at screening and run-in visits entered a 24 Week treatment period and were randomized to receive either Fluticasone furoate/Vilanterol (FF/VI) 100/25 micrograms (mcg) or Fluticasone propionate/salmeterol (FP/S) 250/50mcg or only FP 250mcg followed by a follow-up phase. The total duration for study participation was 30 weeks.

    Pre-assignment
    Screening details
    		 A total of 3162 adult and adolescent participants with asthma were screened, out of which 516 were screen-failures, 1124 were run-in failures, 1522 participants were randomized, and 1504 subjects received at least one dose of study medication to be included in the Intent-to-Treat (ITT) Population.

    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
    		 FF/VI 100/25 mcg once daily
    Arm description
    		 Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fluticasone Furoate/Vilanterol (FF/VI)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    FF/VI 100/25 mcg was administered via inhalation route using ELLIPTA inhaler once daily in the evening.

    Arm title
    		 FP/S 250/50 mcg twice daily
    Arm description
    		 Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fluticasone Propionate/Salmeterol (FP/S)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    FP/S 250/50 mcg was administered via inhalation route using DISKUS/ACCUHALER twice daily; once in the morning and once in the evening.

    Arm title
    		 FP 250 mcg twice daily
    Arm description
    		 Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fluticasone Propionate (FP)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    FP 250 mcg was administered via inhalation route using DISKUS/ACCUHALER twice daily; once in the morning and once in the evening.

    Number of subjects in period 1 [1]
    		FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Started
    504
    501
    499
    Completed
    473
    476
    477
    Not completed
    31
    25
    22
         Consent withdrawn by subject
    15
    12
    11
         Physician decision
    4
    2
    3
         Adverse event, non-fatal
    8
    3
    2
         Lost to follow-up
    -
    2
    2
         Lack of efficacy
    1
    1
    1
         Protocol deviation
    3
    5
    3
    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: A total of 3162 adult and adolescent participants with asthma were screened, out of which 516 were screen-failures, 1124 were run-in failures, 1522 participants were randomized, and 1504 subjects received at least one dose of study medication to be included in the Intent-to-Treat (ITT) Population.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    FF/VI 100/25 mcg once daily
    Reporting group description
    		 Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Reporting group title
    FP/S 250/50 mcg twice daily
    Reporting group description
    		 Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Reporting group title
    FP 250 mcg twice daily
    Reporting group description
    		 Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Reporting group values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily Total
    Number of subjects
    		 504 501 499
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        log mean (standard deviation)
    		 44.4 ± 16.3 43 ± 15.2 43 ± 16.58 -
    Gender categorical
    Units: Subjects
        Female
    		 314 336 314 964
        Male
    		 190 165 185 540
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska native
    		 0 0 1 1
        Asian - East Asian Heritage
    		 8 11 4 23
        Asian- Japanese Heritage
    		 1 0 0 1
        Asian- South East Asian Heritage
    		 1 0 1 2
        Black/African American Heritage
    		 12 14 17 43
        White- Arabic/ North African Heritage
    		 0 1 2 3
        White- White/Caucasian/European Heritage
    		 415 407 410 1232
        White- Mixed White Race
    		 1 0 0 1
        African American/ African and White Heritage
    		 0 5 0 5
        American Indian/Alaskan Native and White Heritage
    		 66 62 64 192
        Asian - East Asian and White Heritage
    		 0 1 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    FF/VI 100/25 mcg once daily
    Reporting group description
    		 Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Reporting group title
    FP/S 250/50 mcg twice daily
    Reporting group description
    		 Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Reporting group title
    FP 250 mcg twice daily
    Reporting group description
    		 Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Primary: Change from Baseline in evening (post meridiem [PM]) Forced Expiratory Volume in one second (FEV1) using Intent-to-Treat (ITT) Population

    		 Close Top of page
    End point title
    		 Change from Baseline in evening (post meridiem [PM]) Forced Expiratory Volume in one second (FEV1) using Intent-to-Treat (ITT) Population
    End point description
    FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the mixed model repeated measures (MMRM) model and least square mean and standard error were calculated. The analysis was performed on ITT Population which comprised of all participants randomized to treatment and who received at least one dose of study medication.
    End point type
    Primary
    End point timeframe
    Baseline and Week 24
    End point values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Number of subjects analysed
    487 [1]
    487 [2]
    479 [3]
    Units: Liter (L)
    least squares mean (standard error)
        Liter (L)
    0.019 ± 0.0107
    0 ± 0.0108
    -0.104 ± 0.0109
    Notes
    [1] - ITT Population
    [2] - ITT Population
    [3] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI 100/25 mcg once daily v FP/S 250/50 mcg twice daily
    Number of subjects included in analysis
    974
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 Least square mean change difference
    Point estimate
    0.019
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.011
         upper limit
    		 0.049
    Notes
    [4] - Non-inferiority was defined if the lower bound of the 95% CI for the difference between mean change from Baseline in clinic visit PM FEV1 for FF/VI and FP/S was more than -100 milliliter (mL)
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/VI 100/25 mcg once daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    966
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least square mean change difference
    Point estimate
    0.123
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.093
         upper limit
    		 0.153
    Notes
    [5] - Inequality
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    FP/S 250/50 mcg twice daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    966
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least square mean change difference
    Point estimate
    0.104
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.074
         upper limit
    		 0.134
    Notes
    [6] - Inequality

    Primary: Change from Baseline in PM FEV1 using Per Protocol (PP) Population

    		 Close Top of page
    End point title
    		 Change from Baseline in PM FEV1 using Per Protocol (PP) Population
    End point description
    FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the MMRM models and least square mean and standard error were calculated. The analysis was performed on PP Population which comprised of all participants in the ITT Population who did not had any full protocol deviations.
    End point type
    Primary
    End point timeframe
    Baseline and Week 24
    End point values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Number of subjects analysed
    425 [7]
    426 [8]
    419 [9]
    Units: Liter (L)
    least squares mean (standard error)
        Liter (L)
    0.02 ± 0.012
    0.014 ± 0.012
    -0.099 ± 0.0121
    Notes
    [7] - PP Population
    [8] - PP Population
    [9] - PP Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI 100/25 mcg once daily v FP/S 250/50 mcg twice daily
    Number of subjects included in analysis
    851
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    Method
    Parameter type
    		 Least square mean change difference
    Point estimate
    0.006
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.027
         upper limit
    		 0.04
    Notes
    [10] - Non-inferiority was defined if the lower bound of the 95% CI for the difference between mean change from Baseline in clinic visit for FF/VI and FP/S was more than -100 mL
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/VI 100/25 mcg once daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    844
    Analysis specification
    Pre-specified
    Analysis type
    		 other [11]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least square mean change difference
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.086
         upper limit
    		 0.153
    Notes
    [11] - Inequality
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FP/S 250/50 mcg twice daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    845
    Analysis specification
    Pre-specified
    Analysis type
    		 other [12]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least square mean change difference
    Point estimate
    0.113
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.08
         upper limit
    		 0.147
    Notes
    [12] - Inequality

    Secondary: Change from Baseline in the percentage of rescue-free 24-hour periods

    		 Close Top of page
    End point title
    		 Change from Baseline in the percentage of rescue-free 24-hour periods
    End point description
    The number of inhalations of rescue medication used during the day and night were recorded by participants using an electronic diary (e-diary). A 24-hour (hr) period in which a participant’s responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1-24
    End point values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Number of subjects analysed
    500 [13]
    498 [14]
    496 [15]
    Units: Percentage of rescue-free 24-hr periods
    least squares mean (standard error)
        Percentage of rescue-free 24-hr periods
    -3 ± 0.62
    -4.2 ± 0.62
    -5.7 ± 0.62
    Notes
    [13] - ITT Population
    [14] - ITT Population
    [15] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI 100/25 mcg once daily v FP/S 250/50 mcg twice daily
    Number of subjects included in analysis
    998
    Analysis specification
    Pre-specified
    Analysis type
    		 other [16]
    Method
    Parameter type
    		 Least square mean change difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 3
    Notes
    [16] - Descriptive
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/VI 100/25 mcg once daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    996
    Analysis specification
    Pre-specified
    Analysis type
    		 other [17]
    P-value
    		 = 0.002
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 4.4
    Notes
    [17] - Inequality
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    FP/S 250/50 mcg twice daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    994
    Analysis specification
    Pre-specified
    Analysis type
    		 other [18]
    P-value
    		 = 0.106
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 3.2
    Notes
    [18] - Inequality

    Secondary: Change from Baseline in the percentage of symptom-free 24-hour periods

    		 Close Top of page
    End point title
    		 Change from Baseline in the percentage of symptom-free 24-hour periods
    End point description
    Change from Baseline in the percentage of symptom-free 24 hour period was evaluated. A 24-hour (hr) period in which a participant’s responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value.Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1-24
    End point values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Number of subjects analysed
    500 [19]
    498 [20]
    496 [21]
    Units: Percentage of symptom-free 24 hour perio
    least squares mean (standard error)
        Percentage of symptom-free 24 hour perio
    -3.5 ± 0.67
    -4.7 ± 0.67
    -6.2 ± 0.67
    Notes
    [19] - ITT Population
    [20] - ITT Population
    [21] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI 100/25 mcg once daily v FP/S 250/50 mcg twice daily
    Number of subjects included in analysis
    998
    Analysis specification
    Pre-specified
    Analysis type
    		 other [22]
    Method
    Parameter type
    		 Least square mean change difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 3.1
    Notes
    [22] - Descriptive
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/VI 100/25 mcg once daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    996
    Analysis specification
    Pre-specified
    Analysis type
    		 other [23]
    P-value
    		 = 0.004
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 4.5
    Notes
    [23] - Inequality
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    FP/S 250/50 mcg twice daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    994
    Analysis specification
    Pre-specified
    Analysis type
    		 other [24]
    P-value
    		 = 0.115
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 3.3
    Notes
    [24] - Inequality

    Secondary: Change from Baseline in morning (ante meridiem [AM]) peak expiratory flow (PEF)

    		 Close Top of page
    End point title
    		 Change from Baseline in morning (ante meridiem [AM]) peak expiratory flow (PEF)
    End point description
    PEF was measured using an electric flow meter each morning. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1-24
    End point values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Number of subjects analysed
    501 [25]
    499 [26]
    497 [27]
    Units: Liter per minute (L/min)
    least squares mean (standard error)
        Liter per minute (L/min)
    8.9 ± 1.48
    3.7 ± 1.49
    -12.6 ± 1.49
    Notes
    [25] - ITT Population
    [26] - ITT Population
    [27] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI 100/25 mcg once daily v FP/S 250/50 mcg twice daily
    Number of subjects included in analysis
    1000
    Analysis specification
    Pre-specified
    Analysis type
    		 other [28]
    Method
    Parameter type
    		 Least square mean change difference
    Point estimate
    5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 9.4
    Notes
    [28] - Descriptive
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/VI 100/25 mcg once daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    998
    Analysis specification
    Pre-specified
    Analysis type
    		 other [29]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    21.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.4
         upper limit
    		 25.6
    Notes
    [29] - Inequality
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    FP/S 250/50 mcg twice daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    996
    Analysis specification
    Pre-specified
    Analysis type
    		 other [30]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    16.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.2
         upper limit
    		 20.4
    Notes
    [30] - Inequality

    Secondary: Percentage of participants with Asthma Control Test (ACT) Score greater than or equal to 20

    		 Close Top of page
    End point title
    		 Percentage of participants with Asthma Control Test (ACT) Score greater than or equal to 20
    End point description
    The ACT was a five-item questionnaire developed as a measure of participant’s asthma control. The percentage of participants controlled, defined as having ACT score greater than or equal to 20 at the end of Week 24 were analyzed using logistic regression model with covariates of Baseline ACT score, region, sex, age and treatment group.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Number of subjects analysed
    471 [31]
    467 [32]
    461 [33]
    Units: Percentage of participants
        Percentage of participants
    92
    93
    91
    Notes
    [31] - ITT Population
    [32] - ITT Population
    [33] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI 100/25 mcg once daily v FP/S 250/50 mcg twice daily
    Number of subjects included in analysis
    938
    Analysis specification
    Pre-specified
    Analysis type
    		 other [34]
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.54
    Notes
    [34] - Descriptive
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/VI 100/25 mcg once daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    932
    Analysis specification
    Pre-specified
    Analysis type
    		 other [35]
    P-value
    		 = 0.595
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.9
    Notes
    [35] - Inequality
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    FP/S 250/50 mcg twice daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    928
    Analysis specification
    Pre-specified
    Analysis type
    		 other [36]
    P-value
    		 = 0.372
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 2.12
    Notes
    [36] - Inequality

    Secondary: Change from Baseline in PM PEF

    		 Close Top of page
    End point title
    		 Change from Baseline in PM PEF
    End point description
    PEF was measured using an electric flow meter each evening. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily PM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1-24
    End point values
    		 FF/VI 100/25 mcg once daily FP/S 250/50 mcg twice daily FP 250 mcg twice daily
    Number of subjects analysed
    501 [37]
    498 [38]
    496 [39]
    Units: L/min
    least squares mean (standard error)
        L/min
    5.5 ± 1.55
    0.5 ± 1.55
    -13.7 ± 1.55
    Notes
    [37] - ITT Population
    [38] - ITT Population
    [39] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    FF/VI 100/25 mcg once daily v FP/S 250/50 mcg twice daily
    Number of subjects included in analysis
    999
    Analysis specification
    Pre-specified
    Analysis type
    		 other [40]
    Method
    Parameter type
    		 Least square mean change difference
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 9.3
    Notes
    [40] - Descriptive
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    FF/VI 100/25 mcg once daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    997
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    19.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.9
         upper limit
    		 23.5
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    FP/S 250/50 mcg twice daily v FP 250 mcg twice daily
    Number of subjects included in analysis
    994
    Analysis specification
    Pre-specified
    Analysis type
    		 other [41]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least square mean change difference
    Point estimate
    14.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.9
         upper limit
    		 18.5
    Notes
    [41] - Inequality

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact one week after completion of study medication (Up to Week 25).
    Adverse event reporting additional description
    AEs and SAEs were collected in ITT Population
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    FF/VI 100/25 mcg once daily
    Reporting group description
    		 Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Reporting group title
    FP 250 mcg twice daily
    Reporting group description
    		 Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Reporting group title
    FP/S 250/50 mcg twice daily
    Reporting group description
    		 Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.

    Serious adverse events
    		 FF/VI 100/25 mcg once daily FP 250 mcg twice daily FP/S 250/50 mcg twice daily
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 504 (1.19%)
    5 / 499 (1.00%)
    4 / 501 (0.80%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive lobular breast carcinoma
         subjects affected / exposed
    1 / 504 (0.20%)
    0 / 499 (0.00%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 504 (0.20%)
    0 / 499 (0.00%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 504 (0.00%)
    1 / 499 (0.20%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 504 (0.00%)
    1 / 499 (0.20%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 504 (0.00%)
    0 / 499 (0.00%)
    1 / 501 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Large intestine perforation
         subjects affected / exposed
    0 / 504 (0.00%)
    0 / 499 (0.00%)
    1 / 501 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 504 (0.00%)
    1 / 499 (0.20%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Vocal cord leukoplakia
         subjects affected / exposed
    0 / 504 (0.00%)
    0 / 499 (0.00%)
    1 / 501 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychotic disorder
         subjects affected / exposed
    0 / 504 (0.00%)
    0 / 499 (0.00%)
    1 / 501 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    1 / 504 (0.20%)
    0 / 499 (0.00%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 504 (0.20%)
    0 / 499 (0.00%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint instability
         subjects affected / exposed
    0 / 504 (0.00%)
    1 / 499 (0.20%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 504 (0.00%)
    1 / 499 (0.20%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 504 (0.20%)
    0 / 499 (0.00%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 504 (0.00%)
    1 / 499 (0.20%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 504 (0.20%)
    0 / 499 (0.00%)
    0 / 501 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 FF/VI 100/25 mcg once daily FP 250 mcg twice daily FP/S 250/50 mcg twice daily
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    126 / 504 (25.00%)
    124 / 499 (24.85%)
    123 / 501 (24.55%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    41 / 504 (8.13%)
    40 / 499 (8.02%)
    37 / 501 (7.39%)
         occurrences all number
    70
    59
    67
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    20 / 504 (3.97%)
    13 / 499 (2.61%)
    10 / 501 (2.00%)
         occurrences all number
    24
    13
    10
    Influenza
         subjects affected / exposed
    9 / 504 (1.79%)
    19 / 499 (3.81%)
    12 / 501 (2.40%)
         occurrences all number
    9
    21
    13
    Nasopharyngitis
         subjects affected / exposed
    61 / 504 (12.10%)
    57 / 499 (11.42%)
    67 / 501 (13.37%)
         occurrences all number
    69
    72
    85
    Pharyngitis
         subjects affected / exposed
    15 / 504 (2.98%)
    18 / 499 (3.61%)
    13 / 501 (2.59%)
         occurrences all number
    18
    20
    14

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Nov 2014
    To increase the minimum age requirement for the participants in the Czech Republic from 12 years and older to 18 years and older
    29 Jan 2015
    To prescribe appropriate asthma treatment to participants who discontinue investigational product (IP) early but elect to continue in the study; In addition, a withdrawal criterion was added to require Investigators to withdraw participants from IP if the participant needs alternative asthma treatment; Additional edits were made to clarify placebo inhaler details, to address rescue medication taken before exercise, and to describe how unblinded participants should be discontinued from IP prior to continuing in the study; Edits were also made to clarify that rescue medication use would be evaluated over a seven day rolling period, that countries will conduct a complete physical exam at Visit 1, that an Interactive Web Response System will be used, and that vital signs will only be databased at Visit 1. Further, edits were made to clarify that daytime symptoms will be evaluated as randomization criteria, that prohibited asthma medications are applicable up until the permanent discontinuation of IP and to remove ‘pre-bronchodilator’ from Inclusion Criteria 4.

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

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

    European Medicines Agency © 1995-Sat Apr 20 03:50:11 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA