Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Exercise Endurance Study to Evaluate the Effects of Treatment of Chronic Obstructive Pulmonary Disease (COPD) Patients With a Dual Bronchodilator: GSK573719/GW642444.Study B (COPD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01323660
Recruitment Status : Completed
First Posted : March 25, 2011
Results First Posted : April 11, 2014
Last Update Posted : February 15, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: GSK573719/GW642444 125/25
Drug: GSK573719/GW642444 62.5/25
Drug: GSK573719 125
Drug: GSK573719 62.5
Drug: GW642444 25
Device: placebo
Enrollment 307
Recruitment Details Participants (par.) who were eligible completed a 12- to 21-day Run-in Period followed by two 12-week treatment (trt) periods.
Pre-assignment Details A total of 634 par. were enrolled and screened, 393 par. entered the Run-in Period, 308 par. were randomized and 307 par. received study trt. Participant Flow data are presented by treatment rather than sequence. Par. received 2 out of the 6 interventions.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC 125/25 µg QD
Hide Arm/Group Description Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 12weeks. Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) QD via a DPI in the morning for 12 weeks. Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks. Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks. Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks. Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Period Title: Treatment Period 1 (12 Weeks)
Started 84 22 24 36 71 70
Completed 65 21 19 31 61 61
Not Completed 19 1 5 5 10 9
Reason Not Completed
Adverse Event             6             1             1             3             3             4
Lack of Efficacy             6             0             2             0             1             3
Protocol Violation             2             0             1             1             1             2
Met Protocol-defined Stopping Criteria             0             0             0             0             1             0
Lost to Follow-up             0             0             0             0             1             0
Withdrawal by Subject             5             0             1             1             3             0
Period Title: Washout Period (14 Days)
Started 65 21 19 31 61 61
Completed 65 [1] 21 [1] 18 [1] 28 [1] 58 [1] 59 [1]
Not Completed 0 0 1 3 3 2
Reason Not Completed
Adverse Event             0             0             0             0             1             0
Lack of Efficacy             0             0             1             3             2             2
[1]
Participants withdrawing during washout are counted under the last treatment taken.
Period Title: Treatment Period 2 (12 Weeks)
Started 67 [1] 18 [1] 17 [1] 28 [1] 59 [1] 58 [1]
Completed 55 17 14 25 55 51
Not Completed 12 1 3 3 4 7
Reason Not Completed
Adverse Event             1             0             0             1             1             2
Lack of Efficacy             9             0             2             2             1             3
Study Closed/Terminated             0             0             0             0             0             1
Lost to Follow-up             1             0             0             0             0             1
Withdrawal by Subject             1             1             1             0             2             0
[1]
“By crossover design, participants were assigned to a different treatment arm in each period.
Arm/Group Title All Study Treatments
Hide Arm/Group Description Participants were randomized to receive a sequence consisting of 2 of the following treatments: UMEC/VI 125/25 µg , UMEC/VI 62.5/25 µg , UMEC 125 µg , UMEC 62.5 µg , VI 25 µg , or placebo QD via a DPI. Each treatment was administered in the morning for 12 weeks. The treatment periods were seperated by 14-day washout period.
Overall Number of Baseline Participants 307
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 307 participants
62.6  (7.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 307 participants
Female
139
  45.3%
Male
168
  54.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 307 participants
African American/African Heritage 6
American Indian or Alaska Native 1
Asian - South East Asian Heritage 1
White - White/Caucasian/European Heritage 298
Mixed Race 1
1.Primary Outcome
Title Change From Baseline in Exercise Endurance Time Post-dose at Week 12 of Each Treatment Period
Hide Description Exercise endurance time (EET) post-dose at Week 12 is defined as the EET obtained 3 hours after dosing at Week 12. EET was measured using the externally paced field walking test called the endurance shuttle walk test (ESWT). Analysis performed using a repeated measures model with covariates of period walking speed, mean walking speed, period, treatment, visit, smoking status, center group, visit by period walking speed, visit by mean walking speed and visit by treatment interactions. The model used all available 3-hour post-dose change from baseline EET values recorded on Day 2, Week 6 and Week 12. Baseline was the EET assessment obtained prior to dosing on Day 1 of each period. The mean walking speed for each participant is the mean of the levels used for the ESWT in each of the two treatment periods. The period walking speed for each participant and treatment period is the difference between the level for that participant and period and the mean walking speed for that participant.
Time Frame Week 12 of each treatment period (up to Study Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Hide Arm/Group Description:
Participants received matching placebo QD via a DPI in the morning for 12 weeks.
Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Participants received VI 25 µg QD via a DPI for 12 weeks.
Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Overall Number of Participants Analyzed 117 37 32 54 115 109
Least Squares Mean (Standard Error)
Unit of Measure: Seconds
0.1  (16.66) 25.1  (30.18) 74.8  (31.58) 30.7  (24.79) 69.5  (17.09) 65.9  (17.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 62.5 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.456
Comments Nominal p-value
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 25.0
Confidence Interval (2-Sided) 95%
-41.0 to 91.0
Estimation Comments Least square mean change difference=UMEC 62.5 µg minus Placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 125 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments Nominal p-value
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 74.7
Confidence Interval (2-Sided) 95%
6.0 to 143.4
Estimation Comments Least square mean change difference=UMEC 125 µg minus Placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, VI 25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.295
Comments Nominal p-value
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 30.6
Confidence Interval (2-Sided) 95%
-26.8 to 88.0
Estimation Comments Least square mean change difference=VI 25 µg minus Placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UMEC 62.5 µg QD, UMEC/VI 62.5/25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.188
Comments Nominal p-value
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 44.4
Confidence Interval (2-Sided) 95%
-21.8 to 110.6
Estimation Comments Least square mean change difference=UMEC/VI 62.5/25 µg minus UMEC 62.5 µg.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection VI 25 µg QD, UMEC/VI 62.5/25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.187
Comments Nominal p-value
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 38.8
Confidence Interval (2-Sided) 95%
-18.9 to 96.5
Estimation Comments Least square mean change difference=UMEC/VI 62.5/25 µg minus VI 25 µg.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection UMEC 125 µg QD, UMEC/VI 125/25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.801
Comments Nominal p-value
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -8.9
Confidence Interval (2-Sided) 95%
-77.8 to 60.1
Estimation Comments Least square mean change difference=UMEC/VI 125/25 µg minus UMEC 125 µg
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection VI 25 µg QD, UMEC/VI 125/25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.233
Comments Nominal p-value
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 35.2
Confidence Interval (2-Sided) 95%
-22.7 to 93.1
Estimation Comments Least square mean change difference=UMEC/VI 125/25 µg minus VI 25 µg.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC/VI 62.5/25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 69.4
Confidence Interval (2-Sided) 95%
24.5 to 114.4
Estimation Comments Least square mean change difference=UMEC/VI 62.5/25 µg minus Placebo.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC/VI 125/25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 65.8
Confidence Interval (2-Sided) 95%
20.3 to 111.3
Estimation Comments Least square mean change difference=UMEC/VI 125/25 µg minus Placebo.
2.Primary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 12 of Each Treatment Period
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 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Clinic visit trough (pre-bronchodilator and pre-dose) FEV1 at Week 12 (Treatment Day 85) is defined as the FEV1 value obtained 24 hours after dosing on Treatment Day 84. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions.
Time Frame Week 12 of each treatment period (up to Study Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Hide Arm/Group Description:
Participants received matching placebo QD via a DPI in the morning for 12 weeks.
Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Participants received VI 25 µg QD via a DPI for 12 weeks.
Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Overall Number of Participants Analyzed 119 38 33 56 117 112
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.043  (0.0156) 0.101  (0.0267) 0.212  (0.0287) 0.069  (0.0222) 0.200  (0.0156) 0.218  (0.0159)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 62.5 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.144
Confidence Interval (2-Sided) 95%
0.086 to 0.203
Estimation Comments Least square mean change difference=UMEC 62.5 µg minus Placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 125 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.255
Confidence Interval (2-Sided) 95%
0.193 to 0.318
Estimation Comments Least square mean change difference=UMEC 125 µg minus Placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, VI 25 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.112
Confidence Interval 95%
0.061 to 0.163
Estimation Comments Least square mean change difference=VI 25 µg minus Placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection UMEC 62.5 µg QD, UMEC/VI 62.5/25 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.099
Confidence Interval (2-Sided) 95%
0.041 to 0.157
Estimation Comments Least square mean change difference=UMEC/VI 62.5/25 µg minus UMEC 62.5 µg.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection VI 25 µg QD, UMEC/VI 62.5/25 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.132
Confidence Interval (2-Sided) 95%
0.081 to 0.183
Estimation Comments Least square mean change difference=UMEC/VI 62.5/25 µg minus VI 25 µg.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection UMEC 125 µg QD, UMEC/VI 125/25 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.849
Comments [Not Specified]
Method Mixed Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.006
Confidence Interval (2-Sided) 95%
-0.055 to 0.067
Estimation Comments Least square mean change difference=UMEC/VI 125/25 µg minus UMEC 125 µg.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection VI 25 µg QD, UMEC/VI 125/25 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.150
Confidence Interval (2-Sided) 95%
0.098 to 0.201
Estimation Comments Least square mean change difference=UMEC/VI 125/25 µg minus VI 25 µg.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC/VI 62.5/25 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.243
Confidence Interval (2-Sided) 95%
0.202 to 0.284
Estimation Comments Least square mean change difference=UMEC/VI 62.5/25 µg minus Placebo.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC/VI 125/25 µg QD
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 Models Analysis
Comments Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.261
Confidence Interval (2-Sided) 95%
0.220 to 0.303
Estimation Comments Least square mean change difference=UMEC/VI 125/25 µg minus Placebo.
3.Secondary Outcome
Title Change From Baseline in Inspiratory Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Hide Description Inspiratory capacity (IC) is defined as the maximum amount of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Baseline is the IC value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough IC is measured pre-dose on Treatment Week 12 of each treatment period. IC 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12 of each treatment period. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. IC measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 12.
Time Frame Week 12 of each treatment period (up to Study Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Hide Arm/Group Description:
Participants received matching placebo QD via a DPI in the morning for 12 weeks.
Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Participants received VI 25 µg QD via a DPI for 12 weeks.
Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Overall Number of Participants Analyzed 120 38 33 56 117 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Trough -0.021  (0.0271) 0.077  (0.0471) 0.216  (0.0505) 0.081  (0.0391) 0.216  (0.0274) 0.204  (0.0281)
3-hours post-dose -0.021  (0.0273) 0.155  (0.0465) 0.208  (0.0498) 0.156  (0.0389) 0.295  (0.0276) 0.312  (0.0283)
4.Secondary Outcome
Title Change From Baseline in Functional Residual Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Hide Description Functional Residual Capacity (FRC) is defined as the amount of air still left in the lungs after breathing out normally. Baseline is the FRC value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough FRC is measured pre-dose on Treatment Week 12. FRC 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. FRC measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 12.
Time Frame Week 12 of each treatment period (up to Study Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Hide Arm/Group Description:
Participants received matching placebo QD via a DPI in the morning for 12 weeks.
Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Participants received VI 25 µg QD via a DPI for 12 weeks.
Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Overall Number of Participants Analyzed 120 38 33 56 117 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Trough -0.083  (0.0460) -0.200  (0.0804) -0.263  (0.0862) -0.218  (0.0666) -0.434  (0.0469) -0.333  (0.0480)
3-hours post-dose -0.094  (0.0461) -0.315  (0.0786) -0.405  (0.0836) -0.431  (0.0654) -0.616  (0.0471) -0.503  (0.0480)
5.Secondary Outcome
Title Change From Baseline in Residual Volume (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Hide Description Residual Volume (RV) is defined as the air that remains in the lungs after breathing out as fully as possible. Baseline is the RV value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough RV is measured pre-dose on Treatment Week 12. RV 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. RV measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 1.
Time Frame Week 12 of each treatment period (up to Study Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Hide Arm/Group Description:
Participants received matching placebo QD via a DPI in the morning for 12 weeks.
Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Participants received VI 25 µg QD via a DPI for 12 weeks.
Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Overall Number of Participants Analyzed 120 38 33 56 117 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Trough -0.049  (0.0491) -0.266  (0.0847) -0.289  (0.0909) -0.291  (0.0705) -0.516  (0.0500) -0.421  (0.0511)
3-hours post-dose -0.071  (0.0495) -0.451  (0.0855) -0.534  (0.0911) -0.483  (0.0711) -0.714  (0.0505) -0.566  (0.0516)
6.Secondary Outcome
Title Change From Baseline in 3-hours Post-dose FEV1 at Week 12 of Each Treatment Period
Hide Description FEVI is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Clinic visit post-dose FEV1 at Week 12 (Treatment Day 85) is defined as the FEV1 value obtained 3 hours after dosing on Treatment Day 85. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions 3 hour post-dose FEV1 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12.
Time Frame Week 12 of each treatment period (up to Study Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Hide Arm/Group Description:
Participants received matching placebo QD via a DPI in the morning for 12 weeks.
Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Participants received VI 25 µg QD via a DPI for 12 weeks.
Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.
Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Overall Number of Participants Analyzed 120 38 33 56 117 110
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.019  (0.0175) 0.168  (0.0296) 0.215  (0.0317) 0.143  (0.0246) 0.297  (0.0175) 0.343  (0.0179)
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported.
Adverse Event Reporting Description SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
 
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Hide Arm/Group Description Participants received matching placebo QD via a DPI in the morning for 12 weeks. Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks. Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks. Participants received VI 25 µg QD via a DPI for 12 weeks. Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks. Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
All-Cause Mortality
Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/151 (2.65%)   1/40 (2.50%)   1/41 (2.44%)   2/64 (3.13%)   3/130 (2.31%)   5/128 (3.91%) 
Gastrointestinal disorders             
Dysphagia  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  1/130 (0.77%)  0/128 (0.00%) 
General disorders             
Chest pain  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  1/128 (0.78%) 
Infections and infestations             
Bronchitis  1  1/151 (0.66%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  0/128 (0.00%) 
Cellulitis  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  1/128 (0.78%) 
Infective exacerbation of chronic obstructive airways diseas  1  1/151 (0.66%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  0/128 (0.00%) 
Subcutaneous abscess  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  1/128 (0.78%) 
Musculoskeletal and connective tissue disorders             
Musculoskeletal pain  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  1/128 (0.78%) 
Osteoarthritis  1  1/151 (0.66%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  0/128 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Bladder cancer  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  1/64 (1.56%)  0/130 (0.00%)  0/128 (0.00%) 
Lung adenocarcinoma  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  1/130 (0.77%)  0/128 (0.00%) 
Lung neoplasm malignant  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  1/130 (0.77%)  0/128 (0.00%) 
Metastases to central nervous system  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  1/130 (0.77%)  0/128 (0.00%) 
Rectal cancer  1  0/151 (0.00%)  0/40 (0.00%)  1/41 (2.44%)  0/64 (0.00%)  0/130 (0.00%)  0/128 (0.00%) 
Nervous system disorders             
IIIrd nerve paresis  1  1/151 (0.66%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  0/128 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Chronic obstructive pulmonary disease  1  1/151 (0.66%)  0/40 (0.00%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  2/128 (1.56%) 
Pulmonary embolism  1  0/151 (0.00%)  1/40 (2.50%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  0/128 (0.00%) 
Skin and subcutaneous tissue disorders             
Leukocytoclastic vasculitis  1  0/151 (0.00%)  0/40 (0.00%)  0/41 (0.00%)  1/64 (1.56%)  0/130 (0.00%)  0/128 (0.00%) 
Vascular disorders             
Deep vein thrombosis  1  0/151 (0.00%)  1/40 (2.50%)  0/41 (0.00%)  0/64 (0.00%)  0/130 (0.00%)  0/128 (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%
Placebo UMEC 62.5 µg QD UMEC 125 µg QD VI 25 µg QD UMEC/VI 62.5/25 µg QD UMEC/VI 125/25 µg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   31/151 (20.53%)   5/40 (12.50%)   14/41 (34.15%)   12/64 (18.75%)   20/130 (15.38%)   18/128 (14.06%) 
Gastrointestinal disorders             
Dyspnoea  1  6/151 (3.97%)  0/40 (0.00%)  1/41 (2.44%)  1/64 (1.56%)  0/130 (0.00%)  1/128 (0.78%) 
Toothache  1  1/151 (0.66%)  0/40 (0.00%)  2/41 (4.88%)  0/64 (0.00%)  1/130 (0.77%)  0/128 (0.00%) 
Infections and infestations             
Nasopharyngitis  1  10/151 (6.62%)  4/40 (10.00%)  4/41 (9.76%)  1/64 (1.56%)  8/130 (6.15%)  2/128 (1.56%) 
Sinusitis  1  3/151 (1.99%)  0/40 (0.00%)  2/41 (4.88%)  3/64 (4.69%)  2/130 (1.54%)  0/128 (0.00%) 
Upper respiratory tract infection  1  1/151 (0.66%)  0/40 (0.00%)  0/41 (0.00%)  2/64 (3.13%)  3/130 (2.31%)  3/128 (2.34%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  2/151 (1.32%)  1/40 (2.50%)  1/41 (2.44%)  0/64 (0.00%)  6/130 (4.62%)  0/128 (0.00%) 
Back pain  1  5/151 (3.31%)  0/40 (0.00%)  1/41 (2.44%)  2/64 (3.13%)  0/130 (0.00%)  2/128 (1.56%) 
Musculoskeletal pain  1  0/151 (0.00%)  0/40 (0.00%)  1/41 (2.44%)  2/64 (3.13%)  0/130 (0.00%)  0/128 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Headache  1  8/151 (5.30%)  1/40 (2.50%)  4/41 (9.76%)  1/64 (1.56%)  3/130 (2.31%)  6/128 (4.69%) 
Cough  1  3/151 (1.99%)  0/40 (0.00%)  1/41 (2.44%)  2/64 (3.13%)  2/130 (1.54%)  5/128 (3.91%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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: NCT01323660    
Other Study ID Numbers: 114418
First Submitted: March 24, 2011
First Posted: March 25, 2011
Results First Submitted: December 19, 2013
Results First Posted: April 11, 2014
Last Update Posted: February 15, 2018