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Study to Compare the Addition of Umeclidinium Bromide (UMEC) to Fluticasone Furoate (FF)/Vilanterol (VI), With Placebo Plus FF/VI in Subjects With Chronic Obstructive Pulmonary Disease (COPD) -Study 2

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ClinicalTrials.gov Identifier: NCT02119286
Recruitment Status : Completed
First Posted : April 21, 2014
Results First Posted : December 12, 2014
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: FF
Drug: VI
Drug: UMEC
Drug: Placebo
Enrollment 620
Recruitment Details Participants ≥ 40 years of age with history of chronic obstructive pulmonary disease (COPD) and a smoking history of ≥ 10 pack-years were enrolled in the study. Participants completed a 4-week run-in period, in which they received fluticasone furoate 100 micrograms(µg)/vilanterol 25 µg, followed by a 12-week treatment period and 1-week follow-up.
Pre-assignment Details A total of 620 participants (pars.) were randomized to study treatment. However, only 619 of these 620 participants compromised the Intent-to-Treat Population, defined as all participants randomized to treatment who received ≥ 1 dose of randomized study medication in the treatment period.
Arm/Group Title FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg
Hide Arm/Group Description Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once-daily (OD) via a dry powder inhaler (DPI), followed by one inhalation of umeclidinium bromide (UMEC) matching placebo, administered via a dry powder inahler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms. Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhalerfollowed by one inhalation of umeclidinium bromide 62.5 µg administered via a dry powder inhaler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms. Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhaler followed by one inhalation of umeclidinium bromide 125 µg administered via a dry powder inhaler in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Period Title: Overall Study
Started 206 206 207
Completed 180 195 200
Not Completed 26 11 7
Reason Not Completed
Adverse Event             9             7             2
Lack of Efficacy             11             3             4
Lost to Follow-up             2             0             1
Withdrawal by Subject             4             1             0
Arm/Group Title FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg Total
Hide Arm/Group Description Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once-daily (OD) via a dry powder inhaler (DPI), followed by one inhalation of umeclidinium bromide (UMEC) matching placebo, administered via a dry powder inahler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms. Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhalerfollowed by one inhalation of umeclidinium bromide 62.5 µg administered via a dry powder inhaler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms. Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhaler followed by one inhalation of umeclidinium bromide 125 µg administered via a dry powder inhaler in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms. Total of all reporting groups
Overall Number of Baseline Participants 206 206 207 619
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 206 participants 206 participants 207 participants 619 participants
62.6  (9.00) 62.6  (8.12) 63.4  (7.49) 62.9  (8.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 206 participants 206 participants 207 participants 619 participants
Female
81
  39.3%
71
  34.5%
76
  36.7%
228
  36.8%
Male
125
  60.7%
135
  65.5%
131
  63.3%
391
  63.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 206 participants 206 participants 207 participants 619 participants
African American/African Heritage 6 6 6 18
Asian - East Asian Heritage 19 25 25 69
White - White/Caucasian/European 180 174 176 530
Mixed Race 1 1 0 2
1.Primary Outcome
Title Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85
Hide 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. Analysis was performed using a mixed model repeated measures (MMRM) with covariates of treatment, Baseline FEV1, smoking status, Day, treatment, Day by baseline interaction and Day by treatment interaction, Day being nominal. Baseline FEV1 is the mean of the two assessments made at 30 and 5 minutes (min) pre-dose on Day 1. The change from baseline value is the difference between the on-treatment value and the baseline value.
Time Frame Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: all pars. randomized to treatment who received ≥ 1 dose of randomized study medication in the Treatment Period. Number of pars. presented represent those with data available at given time point; however, all pars. in the ITT population without missing covariate information, with ≥ 1 post BL measurement are included in the analysis.
Arm/Group Title FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg
Hide Arm/Group Description:
Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once-daily (OD) via a dry powder inhaler (DPI), followed by one inhalation of umeclidinium bromide (UMEC) matching placebo, administered via a dry powder inahler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhalerfollowed by one inhalation of umeclidinium bromide 62.5 µg administered via a dry powder inhaler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhaler followed by one inhalation of umeclidinium bromide 125 µg administered via a dry powder inhaler in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Overall Number of Participants Analyzed 179 195 199
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.030  (0.0110) 0.092  (0.0107) 0.081  (0.0106)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg + Placebo, FF/VI 100/25 µg + UMEC 62.5 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments Restricted maximum likelihood (REM) - based repeated measure approach (MMRM)
Method of Estimation Estimation Parameter Least squared mean difference
Estimated Value 0.122
Confidence Interval (2-Sided) 95%
0.091 to 0.152
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg + Placebo, FF/VI 100/25 µg + UMEC 125 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments Restricted maximum likelihood (REM) - based repeated measure approach (MMRM)
Method of Estimation Estimation Parameter Least squared mean difference
Estimated Value 0.111
Confidence Interval (2-Sided) 95%
0.081 to 0.141
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Weighted Mean (WM), 0-6 Hour FEV1 Obtained Post-dose at Day 84
Hide 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 0-6 hour weighted mean was derived by calculating the area under the FEV1/time curve over the nominal time points of 0 hour (trough value), 15 and 30 min, 1, 3 and 6 hours, using the trapezoidal rule, and then dividing by the actual time between dosing and the 6 hour assessment. Analysis was performed using MMRM with covariates of treatment, Baseline FEV1 (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, Day, and Day by Baseline and Day by treatment interactions. Baseline FEV1 is the mean of the two assessments made at 30 and 5 min pre-dose on Day 1. The change from baseline value is the difference between the on-treatment value and the baseline value.
Time Frame Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post baseline measurement are included in the analysis.
Arm/Group Title FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg
Hide Arm/Group Description:
Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once-daily (OD) via a dry powder inhaler (DPI), followed by one inhalation of umeclidinium bromide (UMEC) matching placebo, administered via a dry powder inahler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhalerfollowed by one inhalation of umeclidinium bromide 62.5 µg administered via a dry powder inhaler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhaler followed by one inhalation of umeclidinium bromide 125 µg administered via a dry powder inhaler in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Overall Number of Participants Analyzed 180 195 199
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.017  (0.0118) 0.164  (0.0115) 0.152  (0.0114)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg + Placebo, FF/VI 100/25 µg + UMEC 62.5 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments Restricted maximum likelihood (REM) - based repeated measure approach (MMRM)
Method of Estimation Estimation Parameter Least squared mean difference
Estimated Value 0.147
Confidence Interval (2-Sided) 95%
0.114 to 0.179
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg + Placebo, FF/VI 100/25 µg + UMEC 125 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments Restricted maximum likelihood (REM) - based repeated measure approach (MMRM)
Method of Estimation Estimation Parameter Least squared mean difference
Estimated Value 0.135
Confidence Interval (2-Sided) 95%
0.103 to 0.167
Estimation Comments [Not Specified]
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks)
Adverse Event Reporting Description On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
 
Arm/Group Title FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg
Hide Arm/Group Description Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once-daily (OD) via a dry powder inhaler (DPI), followed by one inhalation of umeclidinium bromide (UMEC) matching placebo, administered via a dry powder inahler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms. Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhalerfollowed by one inhalation of umeclidinium bromide 62.5 µg administered via a dry powder inhaler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms. Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhaler followed by one inhalation of umeclidinium bromide 125 µg administered via a dry powder inhaler in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
All-Cause Mortality
FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/206 (5.34%)   8/206 (3.88%)   3/207 (1.45%) 
Cardiac disorders       
Myocardial infarction  1  3/206 (1.46%)  2/206 (0.97%)  0/207 (0.00%) 
Atrial fibrillation  1  0/206 (0.00%)  1/206 (0.49%)  0/207 (0.00%) 
Cardiogenic shock  1  0/206 (0.00%)  1/206 (0.49%)  0/207 (0.00%) 
Gastrointestinal disorders       
Gastric ulcer haemorrhage  1  0/206 (0.00%)  1/206 (0.49%)  0/207 (0.00%) 
Infections and infestations       
Pneumonia  1  1/206 (0.49%)  2/206 (0.97%)  0/207 (0.00%) 
Influenza  1  0/206 (0.00%)  1/206 (0.49%)  0/207 (0.00%) 
Injury, poisoning and procedural complications       
Femur fracture  1  0/206 (0.00%)  1/206 (0.49%)  0/207 (0.00%) 
Humerus fracture  1  1/206 (0.49%)  0/206 (0.00%)  0/207 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lung neoplasm  1  0/206 (0.00%)  1/206 (0.49%)  0/207 (0.00%) 
Nervous system disorders       
Cerebral infarction  1  1/206 (0.49%)  0/206 (0.00%)  1/207 (0.48%) 
Cervicobrachial syndrome  1  0/206 (0.00%)  0/206 (0.00%)  1/207 (0.48%) 
Renal and urinary disorders       
Renal aneurysm  1  0/206 (0.00%)  0/206 (0.00%)  1/207 (0.48%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  3/206 (1.46%)  3/206 (1.46%)  1/207 (0.48%) 
Vascular disorders       
Hypertension  1  1/206 (0.49%)  0/206 (0.00%)  0/207 (0.00%) 
Peripheral arterial occlusive disease  1  1/206 (0.49%)  0/206 (0.00%)  0/207 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
FF/VI 100/25 µg + Placebo FF/VI 100/25 µg + UMEC 62.5 µg FF/VI 100/25 µg + UMEC 125 µg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/206 (13.59%)   23/206 (11.17%)   22/207 (10.63%) 
Infections and infestations       
Nasopharyngitis  1  22/206 (10.68%)  11/206 (5.34%)  19/207 (9.18%) 
Musculoskeletal and connective tissue disorders       
Back pain  2  4/206 (1.94%)  8/206 (3.88%)  2/207 (0.97%) 
Nervous system disorders       
Headache  1  5/206 (2.43%)  8/206 (3.88%)  4/207 (1.93%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
2
Term from vocabulary, Back pain
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02119286    
Other Study ID Numbers: 200110
First Submitted: April 17, 2014
First Posted: April 21, 2014
Results First Submitted: December 4, 2014
Results First Posted: December 12, 2014
Last Update Posted: March 23, 2017