ClinicalTrials.gov
ClinicalTrials.gov Menu

GSK573719 Dose Ranging Study in Chronic Obstructive Pulmonary Disease

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: NCT00950807
Recruitment Status : Completed
First Posted : August 3, 2009
Results First Posted : March 4, 2014
Last Update Posted : November 8, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Tiotropium
Drug: Placebo
Drug: GSK573179
Enrollment 176
Recruitment Details  
Pre-assignment Details Participants (par.) who were eligible completed a 4- to 7-day Run-in period prior to randomization. The treatment (trt) phase was comprised of three 14-day trt periods. Par. were randomly assigned to receive a sequence of placebo and 2 of the 9 active trts over the trt phase. Participant Flow data are presented by treatment rather than sequence.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tiotropium 18 µg QD
Hide Arm/Group Description Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days. Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days. Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days. Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days. Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
Period Title: Treatment Period 1
Started 59 13 14 12 13 13 12 14 13 13
Completed 56 13 13 12 12 11 12 14 12 13
Not Completed 3 0 1 0 1 2 0 0 1 0
Reason Not Completed
Lack of Efficacy             1             0             0             0             0             1             0             0             0             0
Protocol Violation             1             0             0             0             0             0             0             0             0             0
Lost to Follow-up             0             0             1             0             0             0             0             0             0             0
Withdrawal by Subject             1             0             0             0             1             0             0             0             1             0
Adverse Event             0             0             0             0             0             1             0             0             0             0
Period Title: Washout Period 1
Started 56 13 13 12 12 11 12 14 12 13
Completed 51 [1] 13 [1] 13 [1] 11 [1] 11 [1] 11 [1] 10 [1] 13 [1] 11 [1] 13 [1]
Not Completed 5 0 0 1 1 0 2 1 1 0
Reason Not Completed
Lack of Efficacy             0             0             0             0             0             0             1             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             0             0             1             0
Protocol-defined Stopping Criteria             3             0             0             0             0             0             1             1             0             0
Adverse Event             2             0             0             1             1             0             0             0             0             0
[1]
Participants withdrawing during washout are counted under the last treatment taken.
Period Title: Treatment Period 2
Started 53 [1] 13 [1] 10 [1] 13 [1] 13 [1] 10 [1] 10 [1] 13 [1] 11 [1] 11 [1]
Completed 51 12 10 12 13 9 9 10 11 11
Not Completed 2 1 0 1 0 1 1 3 0 0
Reason Not Completed
Lack of Efficacy             1             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             1             2             0             0
Protocol-defined Stopping Criteria             1             0             0             0             0             0             0             0             0             0
Adverse Event             0             1             0             1             0             1             0             1             0             0
[1]
By crossover design, participants were assigned to a different treatment arm in each period.
Period Title: Washout Period 2
Started 51 12 10 12 13 9 9 10 11 11
Completed 47 [1] 11 [1] 10 [1] 11 [1] 12 [1] 9 [1] 8 [1] 9 [1] 11 [1] 11 [1]
Not Completed 4 1 0 1 1 0 1 1 0 0
Reason Not Completed
Lack of Efficacy             1             0             0             0             0             0             0             0             0             0
Protocol-defined Stopping Criteria             0             1             0             0             1             0             1             1             0             0
Adverse Event             3             0             0             1             0             0             0             0             0             0
[1]
Participants withdrawing during washout are counted under the last treatment taken.
Period Title: Treatment Period 3
Started 46 [1] 9 [1] 10 [1] 11 [1] 12 [1] 9 [1] 12 [1] 10 [1] 9 [1] 11 [1]
Completed 45 9 10 11 12 9 11 9 9 10
Not Completed 1 0 0 0 0 0 1 1 0 1
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             0             0             0             0             1
Protocol-defined Stopping Criteria             1             0             0             0             0             0             0             1             0             0
Adverse Event             0             0             0             0             0             0             1             0             0             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

The treatment phase was comprised of three 14-day treatment periods, each separated by a 10-14 day washout period. Participants were randomly assigned to receive a sequence of placebo and 2 of the 9 active treatments :

UMEC 62.5, 125, 250, 500, and 1000 µg QD, UMEC 62.5, 125, and 250 µg BID, tiotropium 18 µg QD.

Overall Number of Baseline Participants 176
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants
59.7  (8.12)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants
Female
75
  42.6%
Male
101
  57.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 176 participants
African American/African Heritage 4
White 172
1.Primary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 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 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis were performed using a mixed model with covariates of mean Baseline, period Baseline, treatment and period as fixed effects and participant as a random effect. 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. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.
Time Frame Baseline and Day 15 of each treatment period (up to Study Day 71)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-To-Treat (mITT) Population: all participants randomized to treatment who received at least one dose of study medication. All participants with >=1 post-baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 15.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tio 18 µg QD
Hide Arm/Group Description:
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
Overall Number of Participants Analyzed 150 34 33 35 37 29 31 33 32 34
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.047  (0.017) 0.081  (0.033) 0.099  (0.034) 0.048  (0.033) 0.092  (0.032) 0.138  (0.036) 0.032  (0.035) 0.087  (0.034) 0.124  (0.034) 0.058  (0.033)
Show Statistical Analysis 1 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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.128
Confidence Interval (2-Sided) 95%
0.060 to 0.196
Estimation Comments [Not Specified]
Show Statistical Analysis 2 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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.147
Confidence Interval (2-Sided) 95%
0.077 to 0.216
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 250 µg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.095
Confidence Interval (2-Sided) 95%
0.027 to 0.162
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 500 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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.140
Confidence Interval (2-Sided) 95%
0.074 to 0.205
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 1000 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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.186
Confidence Interval (2-Sided) 95%
0.113 to 0.259
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 62.5 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.079
Confidence Interval (2-Sided) 95%
0.008 to 0.151
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 125 µg BID
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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.134
Confidence Interval (2-Sided) 95%
0.064 to 0.204
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 250 µg BID
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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.172
Confidence Interval (2-Sided) 95%
0.101 to 0.242
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Tio 18 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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.105
Confidence Interval (2-Sided) 95%
0.037 to 0.173
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 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. The weighted mean FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The weighted mean FEV1 was calculated using 0-24 hour (h) post-dose measurements at Day 14 of each treatment period, which included pre-dose and post-dose 1, 3, 6, 9, 12, 13, 15, 18, 21 and 24 hours. Analysis performed using a mixed model with covariates mean BL, period BL, treatment and period as fixed effects and participant as a random effect. BL is the FEV1 value recorded pre-dose on Day 1 of each TP; mean BL is the mean of the BLs for each participant and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.
Time Frame Baseline and Day 14 of each treatment period (TP; up to Study Day 70)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. All participants with >=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 14.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tio 18 µg QD
Hide Arm/Group Description:
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
Overall Number of Participants Analyzed 143 33 33 34 36 29 30 32 31 33
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.059  (0.014) 0.085  (0.025) 0.077  (0.025) 0.077  (0.025) 0.072  (0.024) 0.080  (0.027) 0.062  (0.026) 0.083  (0.025) 0.075  (0.026) 0.069  (0.025)
3.Secondary Outcome
Title Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period
Hide Description Serial FEV1 for OQ dosing is recorded at the pre-AM dose (time 0 h) and at 1, 3, 6, 9, 12,13, 15, 18, 21, 24 and 28 hs after the AM dose on D 14. For BID dosing, the 12 h AM dose corresponds to the pre-PM dose, 13 h AM dose corresponds to the 1 h PM dose, 15 h AM dose corresponds to the 3 h PM dose, 18 h AM corresponds to the 6 h PM dose, 21 h AM dose corresponds to 9 h PM dose, 24 h AM dose corresponds to the 12 h PM dose and 28 h AM dose corresponds to the 16 h PM dose in the table. Analysis performed using a mixed model with covariates of mean BL, period BL, trt, period, time, time by period BL interaction, time by mean BL interaction and time by trt interaction as fixed effects and par. as a random effect. BL is the FEV1 value recorded pre-dose on D 1 of each TP; mean BL is the mean of the BLs for each par. and period BL is the difference between the BL and the mean BL in each TP for each par. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.
Time Frame Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. All par. with >=1 post-BL assessment and non-missing covariate data are included in the analysis. Different par. may have been analyzed at different time points (n=X, X, X, X in the category titles), so the overall number of par. analyzed reflects everyone in the mITT Population with data available at >=1 time point.
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tio 18 µg QD
Hide Arm/Group Description:
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
Overall Number of Participants Analyzed 152 34 33 35 37 30 32 33 32 34
Mean (Standard Deviation)
Unit of Measure: Liters
Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 -0.002  (0.016) 0.140  (0.031) 0.101  (0.032) 0.167  (0.031) 0.095  (0.030) 0.120  (0.033) 0.096  (0.032) 0.139  (0.032) 0.152  (0.032) 0.129  (0.031)
1 hour AM, n=151,34,31,35,37,29,32,33,32,34 0.022  (0.018) 0.246  (0.035) 0.164  (0.037) 0.140  (0.035) 0.056  (0.034) 0.072  (0.038) 0.159  (0.037) 0.132  (0.036) 0.142  (0.037) 0.229  (0.036)
3 hour AM, n=150,34,32,35,37,29,31,33,32,34 -0.003  (0.017) 0.157  (0.034) 0.158  (0.035) 0.222  (0.034) 0.142  (0.033) 0.148  (0.037) 0.153  (0.036) 0.112  (0.035) 0.153  (0.036) 0.191  (0.035)
6 hour AM, n=151,34,33,35,37,30,32,33,31,34 -0.019  (0.016) 0.137  (0.031) 0.114  (0.032) 0.149  (0.031) 0.120  (0.030) 0.105  (0.034) 0.090  (0.033) 0.100  (0.032) 0.141  (0.033) 0.152  (0.032)
9 hour AM, n=149,33,33,34,37,30,31,32,32,33 -0.033  (0.016) 0.121  (0.033) 0.077  (0.033) 0.123  (0.032) 0.118  (0.031) 0.076  (0.035) 0.105  (0.034) 0.104  (0.033) 0.099  (0.034) 0.105  (0.033)
12 hour AM, n=150,34,33,34,37,30,31,32,32,33 -0.068  (0.018) 0.087  (0.035) 0.083  (0.036) 0.084  (0.035) 0.096  (0.034) 0.074  (0.038) 0.058  (0.037) 0.099  (0.036) 0.074  (0.036) 0.153  (0.036)
13 hour AM, n=147,33,33,35,37,29,31,33,32,33 -0.082  (0.016) 0.071  (0.031) 0.077  (0.031) 0.071  (0.031) 0.103  (0.030) 0.096  (0.033) 0.066  (0.032) 0.018  (0.032) 0.048  (0.032) 0.065  (0.031)
15 hour AM, n=151,34,33,35,37,29,30,33,32,34 -0.085  (0.016) 0.074  (0.031) 0.051  (0.032) 0.069  (0.031) 0.038  (0.030) 0.050  (0.033) 0.085  (0.033) 0.054  (0.032) 0.096  (0.032) 0.036  (0.031)
18 hour AM, n=148,33,33,35,36,29,31,33,32,34 -0.145  (0.016) -0.053  (0.033) 0.002  (0.033) -0.018  (0.032) -0.007  (0.031) 0.001  (0.035) -0.020  (0.034) 0.016  (0.033) -0.048  (0.033) -0.097  (0.032)
21 hour AM, n=150,34,33,35,37,29,29,33,32,34 -0.147  (0.017) 0.009  (0.034) 0.035  (0.034) -0.036  (0.034) 0.004  (0.033) 0.006  (0.037) -0.059  (0.036) 0.029  (0.035) -0.005  (0.035) -0.060  (0.034)
24 hour AM, n=150,34,33,35,37,29,31,33,32,34 -0.051  (0.017) 0.067  (0.033) 0.093  (0.034) 0.045  (0.033) 0.088  (0.032) 0.142  (0.036) 0.021  (0.035) 0.091  (0.034) 0.139  (0.035) 0.047  (0.033)
28 hour AM, n=145,34,33,35,37,29,31,33,32,34 0.065  (0.018) 0.179  (0.035) 0.177  (0.036) 0.212  (0.035) 0.143  (0.034) 0.191  (0.038) 0.164  (0.037) 0.219  (0.036) 0.185  (0.037) 0.108  (0.035)
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication up to 10 weeks.
Adverse Event Reporting Description On-treatment AEs and non-serious AEs are reported for members of the mITT Population, comprised of all participants who were randomized to treatment and who had received at least one dose of randomized study medication during treatment period.
 
Arm/Group Title Placebo UMEC 62.5 µg QD UMEC 125 µg QD UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tio 18 µg QD
Hide Arm/Group Description Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days. Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days. Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days. Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days. Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days. Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
All-Cause Mortality
Placebo UMEC 62.5 µg QD UMEC 125 µg QD UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tio 18 µg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo UMEC 62.5 µg QD UMEC 125 µg QD UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tio 18 µg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/158 (0.00%)   0/35 (0.00%)   0/34 (0.00%)   2/36 (5.56%)   0/38 (0.00%)   0/32 (0.00%)   0/34 (0.00%)   1/37 (2.70%)   0/33 (0.00%)   0/35 (0.00%) 
Injury, poisoning and procedural complications                     
Concussion  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  1/36 (2.78%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Chronic obstructive pulmonary disease  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  1/36 (2.78%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  1/37 (2.70%)  0/33 (0.00%)  0/35 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events 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 UMEC 250 µg QD UMEC 500 µg QD UMEC 1000 µg QD UMEC 62.5 µg BID UMEC 125 µg BID UMEC 250 µg BID Tio 18 µg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/158 (6.96%)   2/35 (5.71%)   3/34 (8.82%)   8/36 (22.22%)   9/38 (23.68%)   13/32 (40.63%)   4/34 (11.76%)   4/37 (10.81%)   10/33 (30.30%)   3/35 (8.57%) 
Blood and lymphatic system disorders                     
Thrombocytosis  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  1/32 (3.13%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Gastrointestinal disorders                     
Dry mouth  1  1/158 (0.63%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  1/38 (2.63%)  2/32 (6.25%)  0/34 (0.00%)  1/37 (2.70%)  3/33 (9.09%)  1/35 (2.86%) 
Nausea  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  0/32 (0.00%)  1/34 (2.94%)  0/37 (0.00%)  1/33 (3.03%)  0/35 (0.00%) 
Infections and infestations                     
Nasopharyngitis  1  2/158 (1.27%)  0/35 (0.00%)  0/34 (0.00%)  2/36 (5.56%)  0/38 (0.00%)  4/32 (12.50%)  2/34 (5.88%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Cystitis  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  1/37 (2.70%)  1/33 (3.03%)  0/35 (0.00%) 
Upper respiratory tract infection  1  1/158 (0.63%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  0/37 (0.00%)  1/33 (3.03%)  0/35 (0.00%) 
Injury, poisoning and procedural complications                     
Joint sprain  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  0/37 (0.00%)  1/33 (3.03%)  0/35 (0.00%) 
Investigations                     
Blood potassium increased  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  0/37 (0.00%)  1/33 (3.03%)  0/35 (0.00%) 
Metabolism and nutrition disorders                     
Hyperkalaemia  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  1/32 (3.13%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Arthralgia  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  1/32 (3.13%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Pain in extremity  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  1/32 (3.13%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Nervous system disorders                     
Headache  1  4/158 (2.53%)  1/35 (2.86%)  1/34 (2.94%)  3/36 (8.33%)  1/38 (2.63%)  2/32 (6.25%)  0/34 (0.00%)  1/37 (2.70%)  3/33 (9.09%)  2/35 (5.71%) 
Dysgeusia  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  2/36 (5.56%)  0/38 (0.00%)  2/32 (6.25%)  1/34 (2.94%)  0/37 (0.00%)  2/33 (6.06%)  0/35 (0.00%) 
Migraine  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  0/37 (0.00%)  1/33 (3.03%)  0/35 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Cough  1  1/158 (0.63%)  1/35 (2.86%)  0/34 (0.00%)  1/36 (2.78%)  4/38 (10.53%)  2/32 (6.25%)  0/34 (0.00%)  0/37 (0.00%)  2/33 (6.06%)  0/35 (0.00%) 
Oropharyngeal pain  1  2/158 (1.27%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  1/38 (2.63%)  0/32 (0.00%)  0/34 (0.00%)  1/37 (2.70%)  2/33 (6.06%)  0/35 (0.00%) 
Dysphonia  1  1/158 (0.63%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  2/37 (5.41%)  0/33 (0.00%)  0/35 (0.00%) 
Dyspnoea  1  1/158 (0.63%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  1/38 (2.63%)  1/32 (3.13%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Rhinitis allergic  1  1/158 (0.63%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  1/38 (2.63%)  1/32 (3.13%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Chronic obstructive pulmonary disease  1  0/158 (0.00%)  0/35 (0.00%)  0/34 (0.00%)  0/36 (0.00%)  0/38 (0.00%)  1/32 (3.13%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
Vascular disorders                     
Hypertension  1  0/158 (0.00%)  0/35 (0.00%)  2/34 (5.88%)  1/36 (2.78%)  0/38 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  0/37 (0.00%)  0/33 (0.00%)  0/35 (0.00%) 
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
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00950807     History of Changes
Other Study ID Numbers: 113073
First Submitted: July 30, 2009
First Posted: August 3, 2009
Results First Submitted: January 16, 2014
Results First Posted: March 4, 2014
Last Update Posted: November 8, 2017