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   43846   clinical trials with a EudraCT protocol, of which   7282   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, parallel group study to evaluate the effect of Umeclidinium (UMEC) added to Inhaled corticosteroid/ long-acting beta-agonist combination therapy in subjects with Chronic Obstructive Pulmonary Disease COPD

    Summary
    EudraCT number
    		 2014-000611-14
    Trial protocol
    		 NL   DE   GR   CZ  
    Global end of trial date
    24 Mar 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Mar 2016
    First version publication date
    06 Mar 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    201314
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02257372
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Middlesex, Brentford, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, +1 8664357343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, +1 8664357343,
    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
    19 May 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Mar 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to evaluate the efficacy and safety of the addition of UMEC 62.5mcg once-daily to ICS/LABA therapy, compared with placebo once-daily plus ICS/LABA therapy over 12 weeks in subjects with COPD.
    Protection of trial subjects
    NA
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Sep 2014
    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
    Netherlands: 42
    Country: Number of subjects enrolled
    Czech Republic: 74
    Country: Number of subjects enrolled
    Germany: 101
    Country: Number of subjects enrolled
    Greece: 49
    Worldwide total number of subjects
    266
    EEA total number of subjects
    266
    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)
    128
    From 65 to 84 years
    138
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants had used one of the following inhaled corticosteroids (ICS)/long-acting beta2-agonist (LABA) combinations for at least 30 days prior to Screening: Fluticasone Propionate/Salmeterol (FSC) 500/50 microgram (mcg) twice-daily (bid); budesonide/formoterol 200/6 mcg bid or 400/12 mcg bid; ICS/LABA combinations per study procedures manual.

    Pre-assignment
    Screening details
    		 Participants who met eligibility criteria at screening completed an approximately one week run-in period and participants who met the randomisation criteria were entered a 12-week treatment period. A total of 266 participants with chronic obstructive pulmonary disease (COPD) were screened; 236 participants randomized and entered into 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, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo+ICS/LABA
    Arm description
    		 Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.
    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
    Lactose with magnesium stearate via a DPI once-daily for 12 weeks

    Arm title
    		 Umeclidinium 62.5 mcg+ICS/LABA
    Arm description
    		 Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Umeclidinium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Umeclidinium 62.5microgram (mcg) via a dry powder inhaler (DPI) once-daily for 12 weeks

    Number of subjects in period 1 [1]
    		Placebo+ICS/LABA Umeclidinium 62.5 mcg+ICS/LABA
    Started
    117
    119
    Completed
    110
    109
    Not completed
    7
    10
         Adverse event, serious fatal
    1
    -
         Consent withdrawn by subject
    1
    -
         Adverse event, non-fatal
    2
    7
         Lost to follow-up
    -
    1
         Lack of efficacy
    2
    1
         Protocol deviation
    1
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 266 participants with chronic obstructive pulmonary disease (COPD) were screened; 236 participants randomized and entered into the study.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo+ICS/LABA
    Reporting group description
    		 Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.

    Reporting group title
    Umeclidinium 62.5 mcg+ICS/LABA
    Reporting group description
    		 Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.

    Reporting group values
    		 Placebo+ICS/LABA Umeclidinium 62.5 mcg+ICS/LABA Total
    Number of subjects
    		 117 119 236
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.1 ( 7.86 ) 65.2 ( 7.46 ) -
    Gender categorical
    Units: Subjects
        Female
    		 42 36 78
        Male
    		 75 83 158
    Race, Customized
    Units: Subjects
        Asian - Central/South Asian Heritage
    		 1 0 1
        White - White/Caucasian/European
    		 116 119 235

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo+ICS/LABA
    Reporting group description
    		 Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.

    Reporting group title
    Umeclidinium 62.5 mcg+ICS/LABA
    Reporting group description
    		 Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.

    Primary: Change from Baseline in trough forced expiratory volume in one second (FEV1) on Day 85

    		 Close Top of page
    End point title
    		 Change from Baseline in trough forced expiratory volume in one second (FEV1) on Day 85
    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. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 was measured using spirometry. BL FEV1 is the mean of the two assessments made 30 and 5 minutes (min) pre-dose on Day 1.Change from BL was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis was performed using mixed model repeated measures with covariates of treatment, BL FEV1 (mean of the values measured at 30 min and 5 min pre-dose on Day 1), type of ICS/LABA, smoking status, Day, Day by BL interaction and Day by treatment interaction, where Day is nominal. Intent-to-treat (ITT) population: all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. Only participants with data available at specific timepoint were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (BL) and Day 85
    End point values
    		 Placebo+ICS/LABA Umeclidinium 62.5 mcg+ICS/LABA
    Number of subjects analysed
    110 [1]
    109 [2]
    Units: Liter
        least squares mean (standard error)
    -0.033 ( 0.0184 )
    0.09 ( 0.0183 )
    Notes
    [1] - ITT population
    [2] - ITT population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    UMEC 62.5+ICS/LABA vs. Placebo+ICS/LABA
    Comparison groups
    Placebo+ICS/LABA v Umeclidinium 62.5 mcg+ICS/LABA
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed model repeated measures analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.123
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.071
         upper limit
    		 0.174

    Secondary: Change from Baseline in weighted mean 0-6 hour FEV1 obtained post-dose on Day 84

    		 Close Top of page
    End point title
    		 Change from Baseline in weighted mean 0-6 hour FEV1 obtained post-dose on Day 84
    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 weighted mean FEV1 was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. The weighted mean was calculated by performing six-hour serial spirometry from the pre-dose FEV1 and post-dose FEV1 measurements at 15 minutes, 30 minutes, 1 hour, 3 hours and 6 hours. Baseline FEV1 is the mean of the two assessments made 30 and 5 min pre-dose on Treatment Day 1. Change from Baseline was calculated as weighted mean value on Day 84 minus the Baseline value. Analysis was performed using mixed model repeated measures with covariates of treatment, baseline FEV1 (mean of the values measured at 30 min and 5 min pre-dose on Day 1), type of ICS/LABA , smoking status, Day, Day by baseline interaction and Day by treatment interaction, where Day is nominal.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 84
    End point values
    		 Placebo+ICS/LABA Umeclidinium 62.5 mcg+ICS/LABA
    Number of subjects analysed
    110 [3]
    107 [4]
    Units: Liter
        least squares mean (standard error)
    0.035 ( 0.0175 )
    0.184 ( 0.0176 )
    Notes
    [3] - ITT population. Only participants with data available at specific timepoint were analyzed.
    [4] - ITT population. Only participants with data available at specific timepoint were analyzed.
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    UMEC 62.5+ICS/LABA vs. Placebo+ICS/LABA
    Comparison groups
    Placebo+ICS/LABA v Umeclidinium 62.5 mcg+ICS/LABA
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed model repeated measures analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.148
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.099
         upper limit
    		 0.197

    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 study treatment and until the follow up contact (13 weeks).
    Adverse event reporting additional description
    On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Placebo+ICS/LABA
    Reporting group description
    		 Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.

    Reporting group title
    Umeclidinium 62.5 mcg+ICS/LABA
    Reporting group description
    		 Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.

    Serious adverse events
    		 Placebo+ICS/LABA Umeclidinium 62.5 mcg+ICS/LABA
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 117 (4.27%)
    6 / 119 (5.04%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Road traffic accident
         subjects affected / exposed
    1 / 117 (0.85%)
    0 / 119 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 117 (0.00%)
    1 / 119 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 117 (0.00%)
    1 / 119 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Motor neurone disease
         subjects affected / exposed
    1 / 117 (0.85%)
    0 / 119 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 117 (0.00%)
    1 / 119 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 117 (2.56%)
    3 / 119 (2.52%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 117 (0.00%)
    1 / 119 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 117 (0.00%)
    1 / 119 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Placebo+ICS/LABA Umeclidinium 62.5 mcg+ICS/LABA
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    47 / 117 (40.17%)
    41 / 119 (34.45%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    8 / 117 (6.84%)
    4 / 119 (3.36%)
         occurrences all number
    12
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 117 (4.27%)
    2 / 119 (1.68%)
         occurrences all number
    6
    4
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 117 (4.27%)
    2 / 119 (1.68%)
         occurrences all number
    7
    4
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    17 / 117 (14.53%)
    16 / 119 (13.45%)
         occurrences all number
    23
    18

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Apr 2014
    Brief description of the changes/reason for the amendment: change inclusion criteria 7 from >=70% to <=70%’. This was an administrative change due to symbols change when protocol was made into a PDF
    06 Oct 2014
    Brief description of the changes/reason for amendment: clarified some administrative points
    13 Oct 2014
    Clarify the intent of the study protocol is to include patients who are currently taking the dose and frequency of an ICS/LABA combination approved for COPD

    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-Fri Apr 19 12:42:25 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA