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   43871   clinical trials with a EudraCT protocol, of which   7290   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 Phase IIb, 24 week, randomized, double-blind, 3 arm parallel group study, comparing the efficacy, safety and tolerability of two doses of umeclidinium bromide administered once-daily via a dry powder inhaler, versus placebo, in participants with asthma.

    Summary
    EudraCT number
    		 2016-002843-40
    Trial protocol
    		 PL  
    Global end of trial date
    30 May 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Jun 2019
    First version publication date
    13 Jun 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    205832
    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 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.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
    04 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 May 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effects of Umeclidinium bromide (UMEC) 62.5 mcg and UMEC 31.25 mcg on lung function (trough Forced expiratory volume in 1 second [FEV1]) versus placebo after 24 weeks of treatment.
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Jan 2017
    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
    Canada: 17
    Country: Number of subjects enrolled
    Poland: 107
    Country: Number of subjects enrolled
    Romania: 58
    Country: Number of subjects enrolled
    Russian Federation: 170
    Country: Number of subjects enrolled
    United States: 69
    Worldwide total number of subjects
    421
    EEA total number of subjects
    165
    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)
    365
    From 65 to 84 years
    56
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted at different centers in Russia, United States, Canada, Poland and Romania to compare the efficacy, safety and tolerability of two doses of umeclidinium bromide (UMEC) administered once-daily (OD) via a dry powder inhaler, versus placebo.

    Pre-assignment
    Screening details
    		 Total 421 participants were included in the study.

    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, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo QD
    Arm description
    		 Participants received placebo once daily (QD) via the ELLIPTA dry powder inhaler (DPI) for 24 weeks. Participants also received Fluticasone Furoate (FF) 100 micrograms (mcg) once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Placebo is a white powder administered using ELLIPTA DPI which hold two individual blister strips, both of which contains lactose monohydrate blended with magnesium stearate.

    Investigational medicinal product name
    Fluticasone furoate (FF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    FF is a white powder administered using ELLIPTA DPI which hold two individual blister strips, one of which contains GW685698 blended with lactose monohydrate and another one contains lactose monohydrate with magnesium stearate. This was given 100 mcg once daily as background therapy.

    Arm title
    		 UMEC 31.25 mcg QD
    Arm description
    		 Participants received UMEC 31.25 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    FF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    FF is a white powder administered using ELLIPTA DPI which hold two individual blister strips, one of which contains GW685698 blended with lactose monohydrate and another one contains lactose monohydrate with magnesium stearate. This was given 100 mcg once daily as background therapy.

    Investigational medicinal product name
    UMEC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    UMEC is a white powder administered using ELLIPTA DPI which hold two individual blister strips, one of which contains GSK573719 blended with lactose blended with magnesium stearate and another one contains lactose monohydrate blended with magnesium stearate.

    Arm title
    		 UMEC 62.5 mcg QD
    Arm description
    		 Participants received UMEC 62.5 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    UMEC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    UMEC is a white powder administered using ELLIPTA DPI which hold two individual blister strips, one of which contains GSK573719 blended with lactose blended with magnesium stearate and another one contains lactose monohydrate blended with magnesium stearate.

    Investigational medicinal product name
    FF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    FF is a white powder administered using ELLIPTA DPI which hold two individual blister strips, one of which contains GW685698 blended with lactose monohydrate and another one contains lactose monohydrate with magnesium stearate. This was given 100 mcg once daily as background therapy.

    Number of subjects in period 1
    		Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Started
    143
    139
    139
    Completed
    137
    130
    131
    Not completed
    6
    9
    8
         Consent withdrawn by subject
    1
    5
    4
         Adverse event, non-fatal
    2
    -
    -
         Investigator Site Closed
    1
    2
    -
         Lost to follow-up
    2
    1
    -
         Protocol-Specified Withdrawal Criterion
    -
    -
    1
         Study closed/ Terminated
    -
    -
    1
         Lack of efficacy
    -
    1
    -
         Protocol deviation
    -
    -
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo QD
    Reporting group description
    		 Participants received placebo once daily (QD) via the ELLIPTA dry powder inhaler (DPI) for 24 weeks. Participants also received Fluticasone Furoate (FF) 100 micrograms (mcg) once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Reporting group title
    UMEC 31.25 mcg QD
    Reporting group description
    		 Participants received UMEC 31.25 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Reporting group title
    UMEC 62.5 mcg QD
    Reporting group description
    		 Participants received UMEC 62.5 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Reporting group values
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD Total
    Number of subjects
    		 143 139 139 421
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 126 118 121 365
        From 65-84 years
    		 17 21 18 56
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 49.3 ( 13.93 ) 48.7 ( 15.83 ) 48.5 ( 14.21 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 106 94 98 298
        Male
    		 37 45 41 123
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 10 8 8 26
        Asian, Central/South Asian Heritage
    		 1 1 1 3
        Asian, East Asian Heritage
    		 0 1 0 1
        Asian, South East Asian Heritage
    		 0 1 1 2
        Native Hawaiian or other Pacific Islander
    		 1 0 0 1
        White: Arabic/North African Heritage
    		 0 1 0 1
        White: White/Caucasian/European Heritage
    		 131 126 129 386
        Black or African American & White
    		 0 1 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo QD
    Reporting group description
    		 Participants received placebo once daily (QD) via the ELLIPTA dry powder inhaler (DPI) for 24 weeks. Participants also received Fluticasone Furoate (FF) 100 micrograms (mcg) once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Reporting group title
    UMEC 31.25 mcg QD
    Reporting group description
    		 Participants received UMEC 31.25 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Reporting group title
    UMEC 62.5 mcg QD
    Reporting group description
    		 Participants received UMEC 62.5 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Primary: Mean change from Baseline in clinic trough Forced expiratory volume in 1 second (FEV1) at Week 24

    		 Close Top of page
    End point title
    		 Mean change from Baseline in clinic trough Forced expiratory volume in 1 second (FEV1) at Week 24
    End point description
    FEV1 is measure of lung function,defined as maximal amount of air, can be forcefully exhaled in 1 second.Highest of 3 technically acceptable measurements were recorded at each Visit.Baseline value of clinic FEV1 was last acceptable/borderline acceptable(pre-dose)FEV1 value obtained prior to randomized treatment start date.Change from Baseline was calculated as FEV1 value at Week24 minusFEV1 value at Baseline.Treatment policy estimand was assessed,including all on-/post-treatment data.Intent-to-Treat Population was comprised all randomized participants,excluding who were randomized in error,did not receive the study drug.Different participants may have been analyzed at different timepoints;overall number of participants analyzed reflects everyone in ITT Population without missing covariate information,with Baseline,atleast 1 post-Baseline measurement.Participants with available data at Baseline,atleast 1 timepoint post-Baseline were analyzed.All on-/post-treatment data was included.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1 pre-dose) and Week 24
    End point values
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Number of subjects analysed
    141 [1]
    136 [2]
    139 [3]
    Units: Liters
        least squares mean (standard error)
    0.1289 ( 0.0298 )
    0.3046 ( 0.0304 )
    0.3130 ( 0.0302 )
    Notes
    [1] - ITT Population.
    [2] - ITT Population.
    [3] - ITT Population.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    UMEC 31.25 mcg versus placebo
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    277
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed-model repeated measures (MMRM)
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.1758
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.092
         upper limit
    		 0.2595
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0426
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    UMEC 62.5 mcg versus placebo
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    280
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.1841
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1008
         upper limit
    		 0.2675
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0424

    Secondary: Mean change from Baseline in clinic FEV1 at 3 hours post dose at Week 24

    		 Close Top of page
    End point title
    		 Mean change from Baseline in clinic FEV1 at 3 hours post dose at Week 24
    End point description
    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The highest of 3 technically acceptable measurements were recorded at each Visit. The Baseline value of clinic FEV1 was the last acceptable/borderline acceptable (pre-dose) FEV1 value obtained prior to randomization (either from Visit 2 pre-dose or from Visit 1 pre-bronchodilator). Change from Baseline was calculated as FEV1 value at Week 24 (recorded at 3 hours post dose) minus FEV1 value at Baseline. The analysis only included data collected on-treatment. LS mean change and SE data is presented. Only those participants with available on-treatment data at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 pre-dose) and Week 24
    End point values
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Number of subjects analysed
    133 [4]
    127 [5]
    129 [6]
    Units: Liters
        least squares mean (standard error)
    0.1768 ( 0.0318 )
    0.3663 ( 0.0325 )
    0.3744 ( 0.0322 )
    Notes
    [4] - ITT Population.
    [5] - ITT Population.
    [6] - ITT Population.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    260
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.1895
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 0.2789
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0455
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    UMEC 62.5 mcg vs Placebo
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    262
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [7]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.1976
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1086
         upper limit
    		 0.2866
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0453
    Notes
    [7] - Analysis of covariance (ANCOVA)

    Secondary: Number of participants with on-treatment adverse events (AE), serious adverse events (SAE) and non-serious adverse events (non-SAE)

    		 Close Top of page
    End point title
    		 Number of participants with on-treatment adverse events (AE), serious adverse events (SAE) and non-serious adverse events (non-SAE)
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with on-treatment AEs and SAEs and common (>=3%) non-SAEs have been reported.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Number of subjects analysed
    143 [8]
    139 [9]
    139 [10]
    Units: Participants
        Any AE
    65
    73
    57
        Any SAE
    5
    4
    3
        Any non-SAE
    39
    47
    33
    Notes
    [8] - ITT population.
    [9] - ITT population.
    [10] - ITT population.
    No statistical analyses for this end point

    Secondary: Number of participants with on-treatment abnormal Electrocardiograms (ECG) Findings

    		 Close Top of page
    End point title
    		 Number of participants with on-treatment abnormal Electrocardiograms (ECG) Findings
    End point description
    A single 12-lead ECG and rhythm strip was recorded after measurement of vital signs and spirometry at given time points. All ECG measurements were measured with participants in supine position after >=5 minutes rest. All ECGs were electronically transmitted to an independent and treatment-blinded cardiologist for the measurement. ECG was obtained 15 minutes to 45 minutes after the administration of study treatment. Data for number of participants with abnormal ECG Findings have been reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Week 4 and Week 24
    End point values
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Number of subjects analysed
    143 [11]
    139 [12]
    139 [13]
    Units: Participants
        Week 4, n=139, 135, 138
    23
    26
    35
        Week 24, n=133, 129, 129
    26
    23
    39
    Notes
    [11] - ITT population.
    [12] - ITT population.
    [13] - ITT population.
    No statistical analyses for this end point

    Secondary: Mean Change from Baseline in on-treatment systolic blood pressure (SBP) and diastolic blood pressure (DBP)

    		 Close Top of page
    End point title
    		 Mean Change from Baseline in on-treatment systolic blood pressure (SBP) and diastolic blood pressure (DBP)
    End point description
    Blood pressure was measured at every clinic visit, starting at Visit 1, and prior to conducting spirometry. Blood pressure was measured with participant in sitting position after approximately 5 minutes rest. Baseline value was defined as the latest vital signs assessment prior to randomized treatment start, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the value at specified time point. LS mean and SE data is presented. Different participants may have data available at different time points; thus, the overall number of participants analyzed reflects everyone in the ITT Population without missing covariate information and with a Baseline and at least one post-Baseline measurement. Participants with available data at Baseline and at least one time point post-baseline were analyzed. Participants with data available at the specified time points are represented by n=X in the category titles.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 pre-dose), Weeks 4, 12 and 24
    End point values
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Number of subjects analysed
    139 [14]
    137 [15]
    139 [16]
    Units: Millimeters of mercury
    least squares mean (standard error)
        SBP, Week 4, n=139, 137, 139
    -0.7 ( 0.70 )
    1.1 ( 0.71 )
    0.3 ( 0.70 )
        SBP, Week 12, n=139, 133, 135
    0.3 ( 0.78 )
    -0.2 ( 0.79 )
    0.6 ( 0.79 )
        SBP, Week 24, n=135, 131, 130
    -0.6 ( 0.77 )
    1.1 ( 0.78 )
    -0.1 ( 0.79 )
        DBP, Week 4, n=139, 137, 139
    0.4 ( 0.55 )
    1.2 ( 0.56 )
    0.6 ( 0.55 )
        DBP, Week 12, n=139, 133, 135
    0.7 ( 0.57 )
    0.2 ( 0.59 )
    1.8 ( 0.58 )
        DBP, Week 24, n=135, 131, 130
    -0.1 ( 0.57 )
    1.6 ( 0.58 )
    1.4 ( 0.58 )
    Notes
    [14] - ITT population.
    [15] - ITT population.
    [16] - ITT population.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, SBP, Week 4
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.083
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 3.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, SBP, Week 12
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.636
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.11
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, SBP, Week 24
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.115
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 3.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.1
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    UMEC 62.5 mcg vs Placebo, SBP, Week 4
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.336
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 2.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.99
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    UMEC 62.5 mcg vs Placebo, SBP, Week 12
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.787
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 2.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.11
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    UMEC 62.5 mcg vs Placebo, SBP, Week 24
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.625
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 2.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.1
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, DBP, Week 4
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.309
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 2.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.79
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, DBP, Week 12
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.521
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.82
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, DBP, Week 24
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.047
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 3.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.81
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    UMEC 62.5 mcg versus placebo, DBP, Week 4
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.779
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 1.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.78
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    UMEC 62.5 mcg versus placebo, DBP, Week 12
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.204
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 2.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.82
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    UMEC 62.5 mcg versus placebo, DBP, Week 24
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.066
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 3.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.81

    Secondary: Mean change from Baseline in on-treatment pulse rate

    		 Close Top of page
    End point title
    		 Mean change from Baseline in on-treatment pulse rate
    End point description
    Pulse rate was measured at every clinic visit, starting at Visit 1, and prior to conducting spirometry. Pulse rate was measured with participant in sitting position after approximately 5 minutes rest. Baseline value was defined as the latest vital signs assessment prior to randomized treatment start, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the value at specified time point. LS mean and SE data is presented. Participants with available data at baseline and at least one time point post-baseline were analyzed. Participants with data available at the specified time points are represented by n=X in the category titles.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 pre-dose), Weeks 4, 12 and 24
    End point values
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Number of subjects analysed
    139 [17]
    137 [18]
    139 [19]
    Units: Beats per minute
    least squares mean (standard error)
        Week 4, n=139, 137, 139
    -2.3 ( 0.69 )
    -1.0 ( 0.69 )
    -0.8 ( 0.69 )
        Week 12, n=139, 133, 135
    -0.9 ( 0.59 )
    -0.3 ( 0.60 )
    0.8 ( 0.60 )
        Week 24, n=135, 131, 130
    -1.8 ( 0.75 )
    -0.7 ( 0.76 )
    1.5 ( 0.76 )
    Notes
    [17] - ITT population.
    [18] - ITT population.
    [19] - ITT population.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, Week 4
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.195
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 3.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.97
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, Week 12
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.457
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 2.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.84
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    UMEC 31.25 mcg vs Placebo, Week 24
    Comparison groups
    Placebo QD v UMEC 31.25 mcg QD
    Number of subjects included in analysis
    276
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 3.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.07
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    UMEC 62.5 mcg vs Placebo, Week 4
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 3.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.97
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    UMEC 62.5 mcg versus Placebo, Week 12
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.045
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 3.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.84
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    UMEC 62.5 mcg versus Placebo, Week 24
    Comparison groups
    Placebo QD v UMEC 62.5 mcg QD
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 MMRM
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.3
         upper limit
    		 5.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.07

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events and non-serious adverse events were collected up to 25 weeks.
    Adverse event reporting additional description
    Intent-to-Treat Population was used to collect adverse events.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Placebo QD
    Reporting group description
    		 Participants received placebo once daily (QD) via the ELLIPTA dry powder inhaler (DPI) for 24 weeks. Participants also received Fluticasone Furoate (FF) 100 micrograms (mcg) once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Reporting group title
    UMEC 31.25 mcg QD
    Reporting group description
    		 Participants received UMEC 31.25 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Reporting group title
    UMEC 62.5 mcg QD
    Reporting group description
    		 Participants received UMEC 62.5 mcg once daily via the ELLIPTA DPI for 24 weeks. Participants also received FF 100 mcg once daily as background therapy, in the morning from a separate ELLIPTA DPI for 24 weeks.

    Serious adverse events
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 143 (3.50%)
    4 / 139 (2.88%)
    3 / 139 (2.16%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 143 (1.40%)
    0 / 139 (0.00%)
    0 / 139 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 139 (0.72%)
    0 / 139 (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
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 139 (0.72%)
    0 / 139 (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
    Transient Ischemic attack
         subjects affected / exposed
    1 / 143 (0.70%)
    0 / 139 (0.00%)
    0 / 139 (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
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 143 (0.00%)
    0 / 139 (0.00%)
    1 / 139 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    2 / 143 (1.40%)
    0 / 139 (0.00%)
    1 / 139 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 139 (0.72%)
    0 / 139 (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
    Pulmonary infarction
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 139 (0.72%)
    0 / 139 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 139 (0.72%)
    0 / 139 (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
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 143 (0.00%)
    0 / 139 (0.00%)
    1 / 139 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 143 (0.00%)
    1 / 139 (0.72%)
    0 / 139 (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
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Placebo QD UMEC 31.25 mcg QD UMEC 62.5 mcg QD
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    39 / 143 (27.27%)
    47 / 139 (33.81%)
    33 / 139 (23.74%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 143 (7.69%)
    9 / 139 (6.47%)
    12 / 139 (8.63%)
         occurrences all number
    22
    14
    17
    Gastrointestinal disorders
    Toothache
         subjects affected / exposed
    4 / 143 (2.80%)
    1 / 139 (0.72%)
    5 / 139 (3.60%)
         occurrences all number
    5
    1
    5
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    2 / 143 (1.40%)
    6 / 139 (4.32%)
    4 / 139 (2.88%)
         occurrences all number
    2
    6
    6
    Dysphonia
         subjects affected / exposed
    2 / 143 (1.40%)
    6 / 139 (4.32%)
    0 / 139 (0.00%)
         occurrences all number
    2
    7
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 143 (3.50%)
    3 / 139 (2.16%)
    1 / 139 (0.72%)
         occurrences all number
    5
    3
    1
    Arthralgia
         subjects affected / exposed
    1 / 143 (0.70%)
    5 / 139 (3.60%)
    2 / 139 (1.44%)
         occurrences all number
    1
    6
    2
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    17 / 143 (11.89%)
    14 / 139 (10.07%)
    13 / 139 (9.35%)
         occurrences all number
    21
    20
    15
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 143 (2.10%)
    8 / 139 (5.76%)
    6 / 139 (4.32%)
         occurrences all number
    3
    13
    8
    Respiratory tract infection viral
         subjects affected / exposed
    5 / 143 (3.50%)
    7 / 139 (5.04%)
    4 / 139 (2.88%)
         occurrences all number
    5
    9
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Nov 2016
    Amendment 2: Schedule of Activities (SOA): Included Line item “X” in the box for inclusion/exclusion criteria at Visit 2 (randomization). Section 2: Schedule of Activities (SOA): Included row for “Exacerbation history” and Line item “X” at “screening”. Section 2: Schedule of Activities (SOA): Included row for Exacerbation assessment and line item “X” in the boxes from Visit 2 (randomization) to “end of study (EOS)/early withdrawal (EW)”. Section 2: Schedule of Activities (SOA) [Study Treatment] Included row for dispensing Albuterol/Salbutamol and line item “X” at Visit 1 (screening) until Visit 4. Section 3.3.1 Risk Assessments: Updated the information of hypothalamic pituitary axis (HPA) study (Mentioned 24 hour urinary cortisol Excretion [Previously mentioned as 24 hour serum cortisol excretion]). Section 6.2 Exclusion Criteria: Example of tobacco products has been added to Exclusion criteria #14 Tobacco Use (electronic-cigarettes/vaping). Section 6.2 Exclusion Criteria: Example of a drug has been added to Exclusion criteria 15 Drug/alcohol abuse (marijuana is considered an abused drug). Section 9, Study Assessments and Procedures: Removed: Healthcare Resource Utilization (HRU) from the additional critical Baseline assessments (Screening [Visit 1]). Section 9, Study Assessments and Procedures: Removed: Questionnaires (St. George’s Respiratory Questionnaire ([SGRQ]; Asthma Quality of Life Questionnaire [AQLQ]) from the additional critical Baseline assessments (Screening [Visit 1]). Section 9, Study Assessments and Procedures: Added: Letters “AE” to the additional critical Baseline assessments (Screening [Visit 1]). Section 9.2.1, Time Period and Frequency for collecting adverse event (AE) and serious adverse event (SAE) Information: Updated the information in the second bullet; (Stated AEs will be collected from the start of Study Screening [Previously mentioned AEs will be collected from the start of Study Treatment]).
    06 Jul 2017
    Amendment 2: Table of Contents: Section 7.1.3- Updated Section 7.1.3 to include albuterol/salbutamol medication for Return process, Section 2: Schedule of Activities (SOA) Removed the Screen Run-in “Window” day “-7d”, also added language to clarify when electrocardiogram (ECG) completed: ECG was obtained after the vital signs assessment but prior to performing the pre-bronchodilator spirometry assessment. At all post randomization visits the ECG was to be obtained 15 minutes to 45 minutes after the administration of study treatment. Section 6.1: Inclusion Criteria; inclusion criteria #5: Updated best pre-bronchodilator morning Forced expiratory volume in 1 second (FEV1) to <=90%. Section 6.2.2: Inclusion Criteria for Randomization; inclusion criteria #2: Updated Spirometry: best pre-bronchodilator morning FEV1 to <=90%, Section 6.4 Pre-Screening/Screening/Run-In/Randomization Failures: Updated to Include re-screening language- Re screening of participants will be permitted; however, advance written approval to proceed with rescreening a participant must be obtained from the Medical Monitor. Section 7.1.3: Study Treatment, albuterol/salbutamol, and fluticasone furoate (FF) 100 mcg, Return: Updated to include specifically the medication name, albuterol/salbutamol to the return process. Section 9.1.4: Asthma Exacerbation: Added “moderate” to the last sentence in the paragraph. Section 9.4.3: Electrocardiograms: Added language (“but prior to performing pre-bronchodilator spirometry, assessment”) to clarify when the ECG is to be done.

    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-Wed May 01 21:59:55 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA