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Trial record 30 of 10799 for:    Placebo AND once

A Randomized, Double Blind, Placebo Controlled, Incomplete Block, Crossover, Dose Ranging Study to Evaluate the Dose Response of GSK573719 Administered Once or Twice Daily Over 7 Days in Patients With Chronic Obstructive Pulmonary Disease (COPD) (AC4115321)

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ClinicalTrials.gov Identifier: NCT01372410
Recruitment Status : Completed
First Posted : June 13, 2011
Results First Posted : February 11, 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: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: GSK573719
Drug: Tiotropium
Drug: Placebo
Enrollment 163
Recruitment Details  
Pre-assignment Details Participants were randomized to receive a sequence of 3 of 8 possible treatments over 3 treatment periods. There are 56 combinations of 3 treatments from the 8 study treatments, each of which can be ordered in 6 ways (totaling 336 possible sequences; 163 were randomly assigned). Participant Flow data are presented by treatment rather than sequence.
Arm/Group Title Placebo UMEC 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 µg BID TIO 18 µg QD
Hide Arm/Group Description Participants received matching placebo once in the morning and once in the evening for 7 days via a dry powder inhaler (DPI) in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of umeclidinium bromide (UMEC) 15.6 micrograms (µg) once a day (QD) for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 62.5 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 125 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 15.6 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received tiotropium bromide (TIO) 18 µg inhalation capsules via the HandiHaler dry powder inhaler for 7 days in the morning and placebo via the DPI in the evening in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Period Title: Treatment Period 1 (7 Days)
Started 20 21 19 20 21 21 22 19
Completed 19 19 19 20 19 21 20 19
Not Completed 1 2 0 0 2 0 2 0
Reason Not Completed
Lack of Efficacy             1             1             0             0             1             0             0             0
Adverse Event             0             1             0             0             0             0             1             0
Lost to Follow-up             0             0             0             0             1             0             0             0
Participant Withdrew Consent             0             0             0             0             0             0             1             0
Period Title: Washout Period 1 (10-14 Days)
Started 19 19 19 20 19 21 20 19
Completed 18 [1] 19 [1] 19 [1] 20 [1] 19 [1] 21 [1] 20 [1] 18 [1]
Not Completed 1 0 0 0 0 0 0 1
Reason Not Completed
Participant Withdrew Consent             1             0             0             0             0             0             0             1
[1]
Participants withdrawing during washout are counted under the last treatment taken.
Period Title: Treatment Period 2 (7 Days)
Started 19 [1] 21 [1] 22 [1] 17 [1] 19 [1] 16 [1] 21 [1] 19 [1]
Completed 19 21 22 17 19 16 21 19
Not Completed 0 0 0 0 0 0 0 0
[1]
By crossover design, participants were assigned to a different treatment arm in each period.
Period Title: Washout Period 2 (10-14 Days)
Started 19 21 22 17 19 16 21 19
Completed 19 [1] 21 [1] 22 [1] 17 [1] 17 [1] 16 [1] 20 [1] 17 [1]
Not Completed 0 0 0 0 2 0 1 2
Reason Not Completed
Adverse Event             0             0             0             0             1             0             0             0
Participant Withdrew Consent             0             0             0             0             1             0             1             1
Lack of Efficacy             0             0             0             0             0             0             0             1
[1]
Participants withdrawing during washout are counted under the last treatment taken.
Period Title: Treatment Period 3 (7 Days)
Started 21 [1] 18 [1] 16 [1] 22 [1] 20 [1] 19 [1] 15 [1] 18 [1]
Completed 21 18 15 22 20 18 15 18
Not Completed 0 0 1 0 0 1 0 0
Reason Not Completed
Adverse Event             0             0             1             0             0             0             0             0
Protocol Deviation             0             0             0             0             0             1             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 Participants received a sequence containing 3 of the following 8 possible treatments: placebo; UMEC 15.6 µg, 31.25 µg, 62.5 µg, and 125 µg QD; UMEC 15.6 µg and 31.25 µg BID; TIO 18 µg QD. Participants received each of the treatments in 1 of 3 7-day treatment periods, each of which was followed by a Washout Period. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Overall Number of Baseline Participants 163
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 163 participants
59.5  (9.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants
Female
85
  52.1%
Male
78
  47.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 163 participants
African American/African Heritage 16
American Indian or Alaska Native 1
White - White/Caucasian/European Heritage 145
Mixed Race 1
1.Primary Outcome
Title Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)
Hide Description The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate trough FEV1dose response. The Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed separately and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. The fixed-effects parameters of the dose response model include Emax (the maximum predicted FEV1 response), ED50 (potency), and S0 (estimated Baseline FEV1). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Data for Emax and S0 are reported in this table. mITT=Modified Intent-to-Treat; par.=participants; BL=Baseline.
Time Frame Day 7 and Day 8 of each treatment period (up to Study Day 50)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population: par. randomized to treatment who received >=1 dose of study medication. 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 in category titles); the overall number of par. analyzed reflects everyone in the mITT Population.
Arm/Group Title All Study Treatments
Hide Arm/Group Description:
Participants received a sequence containing 3 of the following 8 possible treatments: placebo; UMEC 15.6 µg, 31.25 µg, 62.5 µg, and 125 µg QD; UMEC 15.6 µg and 31.25 µg BID; TIO 18 µg QD. Participants received each of the treatments in 1 of 3 7-day treatment periods, each of which was followed by a Washout Period. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Overall Number of Participants Analyzed 163
Geometric Mean (95% Confidence Interval)
Unit of Measure: Liters
Day 8, Emax, n=157
0.185
(0.154 to 0.216)
Pooled Day 7 and Day 8, Emax, n=160
0.156
(0.123 to 0.189)
Day 8, S0, n=157
1.24
(1.21 to 1.27)
Pooled Day 7 and 8, S0, n=160
1.24
(1.21 to 1.27)
2.Primary Outcome
Title Final Dose-response Model for Trough FEV1 for ED50 (Potency) Parameter
Hide Description The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate dose response. Both a Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. ED50 is defined as the potency and is the dose that yields 50% of Emax (maximum predicted FEV1 response). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
Time Frame Day 7 and Day 8 of each treatment period (up to Study Day 50)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population: par. randomized to treatment who received >=1 dose of study medication. 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 in category titles); the overall number of par. analyzed reflects everyone in the mITT Population.
Arm/Group Title All Study Treatments
Hide Arm/Group Description:
Participants received a sequence containing 3 of the following 8 possible treatments: placebo; UMEC 15.6 µg, 31.25 µg, 62.5 µg, and 125 µg QD; UMEC 15.6 µg and 31.25 µg BID; TIO 18 µg QD. Participants received each of the treatments in 1 of 3 7-day treatment periods, each of which was followed by a Washout Period. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Overall Number of Participants Analyzed 163
Geometric Mean (95% Confidence Interval)
Unit of Measure: micrograms
Day 8, ED50, n=157
37.4
(17.8 to 57.0)
Pooled Day 7 and Day 8, ED50, n=160
38.2
(14.7 to 61.7)
3.Primary Outcome
Title Final Dose-response Model Parameter β-FEV1MB-S0 for Trough FEV1
Hide Description The trough FEV1 data for both the once-daily (QD) and twice-daily (BID) UMEC doses were included in a parametric analysis in order to evaluate dose response. Both a Day 8 dataset and a pooled dataset for Day 7 and Day 8 were analyzed and reported. The rationale for pooling Day 7 and Day 8 (post-hoc analysis) was to ensure informative interpretation of FEV1 response as a function of dose given the repeated measures for trough FEV1 response within each participant on different days. β-FEV1MB-S0 is defined as the covariate (Baseline trough FEV1) effect on the mean Baseline trough FEV1 estimate (S0). FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
Time Frame Day 7 and Day 8 of each treatment period (up to Study Day 50)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population: par. randomized to treatment who received >=1 dose of study medication. 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 in category titles); the overall number of par. analyzed reflects everyone in the mITT Population.
Arm/Group Title All Study Treatments
Hide Arm/Group Description:
Participants received a sequence containing 3 of the following 8 possible treatments: placebo; UMEC 15.6 µg, 31.25 µg, 62.5 µg, and 125 µg QD; UMEC 15.6 µg and 31.25 µg BID; TIO 18 µg QD. Participants received each of the treatments in 1 of 3 7-day treatment periods, each of which was followed by a Washout Period. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Overall Number of Participants Analyzed 163
Measure Type: Number
Unit of Measure: fraction of mean estimated Baseline FEV1
Day 8, βFEV1MB-S0, n=157 0.691
Pooled Day 7 and 8, βFEV1MB-S0, n=160 0.686
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Study Treatments
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Day 8 analysis.
Method Wald Test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Study Treatments
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Pooled Day 7 and 8 analysis.
Method Wald Test
Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 8 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 8 is defined as the value obtained 24 hours after the morning dose administered on Day 7. Analysis was 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 particiapant. Change from Baseline for each treatment period is the trough FEV1 at Day 8 minus the Baseline value for that treatment period.
Time Frame Baseline and Day 8 of each treatment period (up to Study Day 50)
Hide 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 8.
Arm/Group Title Placebo UMEC 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 µg BID TIO 18 µg QD
Hide Arm/Group Description:
Participants received matching placebo once in the morning and once in the evening for 7 days via a dry powder inhaler (DPI) in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of umeclidinium bromide (UMEC) 15.6 micrograms (µg) once a day (QD) for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 62.5 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 125 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 15.6 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received tiotropium bromide (TIO) 18 µg inhalation capsules via the HandiHaler dry powder inhaler for 7 days in the morning and placebo via the DPI in the evening in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Overall Number of Participants Analyzed 59 58 56 59 59 55 57 56
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.074  (0.022) 0.038  (0.022) 0.027  (0.023) 0.049  (0.022) 0.109  (0.022) 0.051  (0.023) 0.065  (0.023) 0.027  (0.023)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 15.6 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 0.113
Confidence Interval (2-Sided) 95%
0.058 to 0.168
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 31.25 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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.101
Confidence Interval (2-Sided) 95%
0.045 to 0.158
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 0.124
Confidence Interval (2-Sided) 95%
0.068 to 0.179
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.183
Confidence Interval (2-Sided) 95%
0.127 to 0.239
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 15.6 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 0.125
Confidence Interval (2-Sided) 95%
0.069 to 0.182
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 31.25 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 0.139
Confidence Interval (2-Sided) 95%
0.083 to 0.196
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
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 <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.101
Confidence Interval (2-Sided) 95%
0.045 to 0.157
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline (BL) in Serial FEV1 Over Time on Day 7 of Each Treatment Period
Hide Description Serial FEV1 for once daily dosing is recorded at the pre-AM dose (AMD; time 0 hour [h]) and at 1, 3, 6, 9, 12,13, 15, 23, and 24 hours after the AMD on Day 7. For twice daily dosing, the 12 h AMD corresponds to the pre-PM dose (PMD), the 13 h AMD corresponds to the 1 h PMD, the 15 h AMD corresponds to the 3 h PMD, the 23 h AMD corresponds to the 11 h PMD, and the 24 h AMD corresponds to the 12 h PMD in this table. Analysis was performed using a mixed model with covariates of mean BL, period BL, treatment, period, time, time by period BL interaction, time by mean BL interaction, and time by treatment interaction as fixed effects and participant as a random effect. BL is the value recorded pre-dose on Day 1 of each TP, mean BLis 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 timepoint within a TP is the serial FEV1 measure at that timepoint minus the BL value for that TP.
Time Frame Baseline and Day 7 of each treatment period (TP; up to Study Day 49)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. All participants (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 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 µg BID TIO 18 µg QD
Hide Arm/Group Description:
Participants received matching placebo once in the morning and once in the evening for 7 days via a dry powder inhaler (DPI) in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of umeclidinium bromide (UMEC) 15.6 micrograms (µg) once a day (QD) for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 62.5 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 125 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 15.6 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received tiotropium bromide (TIO) 18 µg inhalation capsules via the HandiHaler dry powder inhaler for 7 days in the morning and placebo via the DPI in the evening in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Overall Number of Participants Analyzed 60 59 56 59 60 55 57 56
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Pre-AMD, n=59, 58, 55, 59, 60, 54, 57, 54 -0.007  (0.021) 0.068  (0.021) 0.067  (0.021) 0.065  (0.021) 0.122  (0.021) 0.069  (0.022) 0.097  (0.021) 0.084  (0.022)
1 h AMD, n=59, 59, 56, 59, 60, 55, 57, 56 -0.006  (0.023) 0.086  (0.023) 0.112  (0.023) 0.107  (0.023) 0.167  (0.023) 0.128  (0.024) 0.135  (0.023) 0.176  (0.023)
3 h AMD, n=59, 59, 56, 59, 59, 55, 57, 56 -0.013  (0.024) 0.082  (0.024) 0.132  (0.024) 0.082  (0.024) 0.176  (0.024) 0.126  (0.025) 0.120  (0.024) 0.180  (0.025)
6 h AMD, n=59, 59, 55, 59, 59, 55, 57, 56 -0.054  (0.022) 0.056  (0.022) 0.067  (0.022) 0.056  (0.022) 0.088  (0.022) 0.045  (0.022) 0.081  (0.022) 0.128  (0.022)
9 h AMD, n=59, 59, 56, 59, 58, 55, 56, 56 -0.072  (0.022) 0.040  (0.022) 0.050  (0.022) 0.084  (0.022) 0.132  (0.022) 0.070  (0.023) 0.038  (0.022) 0.094  (0.023)
12 h AMD/Pre-PMD, n=59, 59, 56, 59, 59, 55, 57, 56 -0.086  (0.023) 0.022  (0.023) 0.028  (0.023) 0.043  (0.023) 0.103  (0.023) 0.048  (0.023) 0.048  (0.023) 0.081  (0.023)
13 h AMD/1 h PMD, n=59, 59, 56, 59, 58, 55, 57, 56 -0.085  (0.024) -0.001  (0.024) -0.003  (0.024) 0.026  (0.024) 0.103  (0.024) 0.063  (0.025) 0.041  (0.024) 0.061  (0.025)
15 h AMD/3 h PMD, n=59, 58, 56, 58, 59, 55, 57, 56 -0.112  (0.023) -0.008  (0.023) 0.004  (0.023) 0.022  (0.023) 0.073  (0.023) 0.041  (0.024) 0.047  (0.023) 0.037  (0.023)
23 h AMD/11 h PMD, n=59, 57, 56, 59, 59, 55, 57,56 -0.101  (0.024) 0.006  (0.025) -0.006  (0.025) 0.012  (0.024) 0.073  (0.024) 0.001  (0.025) 0.33  (0.025) 0.002  (0.025)
24 h AMD/12 h PMD, n=59, 58, 56, 59, 59, 55, 57,56 -0.065  (0.024) 0.070  (0.024) 0.065  (0.024) 0.067  (0.023) 0.146  (0.024) 0.083  (0.024) 0.084  (0.024) 0.049  (0.024)
6.Secondary Outcome
Title Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours After the Morning Dosing on Day 7 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 post-dose measurements at Day 7 of each treatment period, which included pre-dose and post-dose 1, 3, 6, 9, 12, 13, 15, 23, and 24 hours. Analysis was performed using a mixed model with covariates of 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 weighted mean FEV1 at Day 7 minus the BL value for that TP.
Time Frame Baseline and Day 7 of each treatment period (TP; up to Study Day 49)
Hide 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 7.
Arm/Group Title Placebo UMEC 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 µg BID TIO 18 µg QD
Hide Arm/Group Description:
Participants received matching placebo once in the morning and once in the evening for 7 days via a dry powder inhaler (DPI) in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of umeclidinium bromide (UMEC) 15.6 micrograms (µg) once a day (QD) for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 62.5 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 125 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 15.6 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Participants received tiotropium bromide (TIO) 18 µg inhalation capsules via the HandiHaler dry powder inhaler for 7 days in the morning and placebo via the DPI in the evening in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
Overall Number of Participants Analyzed 54 56 51 54 56 52 55 53
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.074  (0.018) 0.043  (0.018) 0.045  (0.019) 0.059  (0.018) 0.100  (0.018) 0.062  (0.018) 0.068  (0.018) 0.084  (0.018)
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 7 weeks), are reported.
Adverse Event Reporting Description On-treatment SAEs and non-serious AEs were reported for members of the mITT Population, comprised of all participants who were randomized to treatment who had received at least one dose of study medication.
 
Arm/Group Title Placebo UMEC 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 µg BID TIO 18 µg QD
Hide Arm/Group Description Participants received matching placebo once in the morning and once in the evening for 7 days via a dry powder inhaler (DPI) in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of umeclidinium bromide (UMEC) 15.6 micrograms (µg) once a day (QD) for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 62.5 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 125 µg QD for 7 days in the morning, and matching placebo QD for 7 days in the evening, via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 15.6 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received an inhaled dose of a dry powder formulation of UMEC 31.25 µg once in the morning and once in the evening for 7 days via a DPI in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call. Participants received tiotropium bromide (TIO) 18 µg inhalation capsules via the HandiHaler dry powder inhaler for 7 days in the morning and placebo via the DPI in the evening in one of three 7-day treatment periods. Treatment Periods 1 and 2 were followed by a 10- to 14-day Washout Period; Treatment Period 3 was followed by a 7- to 9-day Washout Period before the follow-up phone call.
All-Cause Mortality
Placebo UMEC 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 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 (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo UMEC 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 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 (%)
Total   0/60 (0.00%)   1/60 (1.67%)   1/57 (1.75%)   0/59 (0.00%)   0/60 (0.00%)   0/56 (0.00%)   0/58 (0.00%)   0/56 (0.00%) 
Cardiac disorders                 
Myocardial infarction  1  0/60 (0.00%)  0/60 (0.00%)  1/57 (1.75%)  0/59 (0.00%)  0/60 (0.00%)  0/56 (0.00%)  0/58 (0.00%)  0/56 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Acute respiratory failure  1  0/60 (0.00%)  1/60 (1.67%)  0/57 (0.00%)  0/59 (0.00%)  0/60 (0.00%)  0/56 (0.00%)  0/58 (0.00%)  0/56 (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 15.6 µg QD UMEC 31.25 µg QD UMEC 62.5 µg QD UMEC 125 µg QD UMEC 15.6 µg BID UMEC 31.25 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 (%)
Total   2/60 (3.33%)   3/60 (5.00%)   0/57 (0.00%)   0/59 (0.00%)   8/60 (13.33%)   4/56 (7.14%)   1/58 (1.72%)   2/56 (3.57%) 
Infections and infestations                 
Nasopharyngitis  1  0/60 (0.00%)  1/60 (1.67%)  0/57 (0.00%)  0/59 (0.00%)  1/60 (1.67%)  0/56 (0.00%)  0/58 (0.00%)  2/56 (3.57%) 
Sinusitis  1  0/60 (0.00%)  0/60 (0.00%)  0/57 (0.00%)  0/59 (0.00%)  2/60 (3.33%)  0/56 (0.00%)  0/58 (0.00%)  0/56 (0.00%) 
Nervous system disorders                 
Headache  1  2/60 (3.33%)  1/60 (1.67%)  0/57 (0.00%)  0/59 (0.00%)  3/60 (5.00%)  4/56 (7.14%)  1/58 (1.72%)  0/56 (0.00%) 
Dysgeusia  1  0/60 (0.00%)  1/60 (1.67%)  0/57 (0.00%)  0/59 (0.00%)  2/60 (3.33%)  0/56 (0.00%)  0/58 (0.00%)  0/56 (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: NCT01372410     History of Changes
Other Study ID Numbers: 115321
First Submitted: June 9, 2011
First Posted: June 13, 2011
Results First Submitted: December 19, 2013
Results First Posted: February 11, 2014
Last Update Posted: November 8, 2017