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GSK573719 Dose Ranging Study in Chronic Obstructive Pulmonary Disease

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT00950807
Collaborator
(none)
176
Enrollment
19
Locations
10
Arms
6.4
Duration (Months)
9.3
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will evaluate the dose response, safety, and pharmacokinetics of GSK573719 compared with placebo in subjects with COPD.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, incomplete block design study to evaluation of 5 doses of GSK573719 administered once-daily and 3 doses of GSK573719 administered twice-daily over 14 days in subjects with COPD and will include tiotropium as an open-label active control. The pharmacokinetic profile of GSK573719 will also be evaluated.

Study Design

Study Type:
Interventional
Actual Enrollment :
176 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of GSK573719 Administered Once- and Twice-Daily in Subjects With COPD
Study Start Date :
Sep 1, 2009
Actual Primary Completion Date :
Mar 1, 2010
Actual Study Completion Date :
Mar 15, 2010

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Placebo

Drug: Placebo
Inactive/ excipients only
Active Comparator: Tiotropium

Tiotropium

Drug: Tiotropium
long-acting muscarinic receptor antagonist; 18mcg once-daily
Experimental: Arm 1

GSK573719 1000mcg once daily

Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 2

GSK573719 500mcg once daily

Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 3

GSK573719 250mcg once daily

Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 4

GSK573719 125mcg once daily

Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 5

GSK573719 62.5 mcg once daily

Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 6

GSK573719 250mcg twice daily

Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 7

GSK573719 125mcg twice daily

Drug: GSK573179
GSK573179 investigational drug
Experimental: Arm 8

GSK573719 62.5mcg twice daily

Drug: GSK573179
GSK573179 investigational drug

Outcome Measures

Primary Outcome Measures

  1. Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period [Baseline and Day 15 of each treatment period (up to Study Day 71)]

    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.

Secondary Outcome Measures

  1. Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period [Baseline and Day 14 of each treatment period (TP; up to Study Day 70)]

    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.

  2. Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period [Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70)]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
40 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • A signed and dated written informed consent prior to study participation

  • Males or females of non-childbearing potential

  • 40 to 80 years of age

  • COPD diagnosis

  • 10 pack-years history or greater of cigarette smoking

  • Post-bronchodilator FEV1/FVC ratio of 0.70 or less

  • Post-bronchodilator FEV1 of 35 to 70% of predicted normal

Exclusion Criteria:

  • Asthma

  • Other significant respiratory disorders besides COPD, including alpha-1 deficiency

  • Previous lung resection surgery

  • Use of oral steroids or antibiotics for a COPD exacerbation within 6 weeks of screening

  • Hospitalization for COPD or pneumonia within 3 months of screening

  • Any significant disease that would put subject at risk through study participation

  • BMI greater than 35

  • Pacemaker

  • Significantly abnormal ECG, Holter, or clinical lab finding (including Hepatitis B or

  • Cancer

  • Allergy or hypersensitivity to anticholinergics or inhaler excipients

  • Diseases that would contra-indicate the use of anticholinergics

  • Use of oral corticosteroids within 6 weeks of screening

  • Use of long-acting beta-agonists within 48 hours of screening

  • Use of tiotropium within 14 days of screening

  • Use of theophyllines or anti-leukotrienes within 48 hours of screening

  • Use of short-acting bronchodilators within 4 to 6 hours of screening

  • Use of investigational medicines within 30 days of screening

  • Use of high dose inhaled corticosteroids

  • Use of long-term oxygen therapy, CPAP or NIPPV

  • Previous use of GSK573719

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Phoenix Arizona United States 85013
2 GSK Investigational Site San Diego California United States 92117
3 GSK Investigational Site Upland California United States 91786
4 GSK Investigational Site Cincinnati Ohio United States 45231
5 GSK Investigational Site Easley South Carolina United States 29640
6 GSK Investigational Site Gaffney South Carolina United States 29340
7 GSK Investigational Site Greenville South Carolina United States 29615
8 GSK Investigational Site Seneca South Carolina United States 29678
9 GSK Investigational Site Spartanburg South Carolina United States 29303
10 GSK Investigational Site Union South Carolina United States 29379
11 GSK Investigational Site Frankfurt Hessen Germany 60596
12 GSK Investigational Site Wiesbaden Hessen Germany 65187
13 GSK Investigational Site Hannover Niedersachsen Germany 30159
14 GSK Investigational Site Mainz Rheinland-Pfalz Germany 55131
15 GSK Investigational Site Magdeburg Sachsen-Anhalt Germany 39112
16 GSK Investigational Site Grosshansdorf Schleswig-Holstein Germany 22927
17 GSK Investigational Site Berlin Germany 10787
18 GSK Investigational Site Berlin Germany 13125
19 GSK Investigational Site Hamburg Germany 20253

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00950807
Other Study ID Numbers:
  • 113073
First Posted:
Aug 3, 2009
Last Update Posted:
Nov 8, 2017
Last Verified:
Oct 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
Dose ranging
Chronic Bronchitis
Long-acting muscarinic antagonist
cross-over
COPD
Emphysema
Chronic Obstructive Pulmonary Disease (COPD)
anticholinergic
Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Tiotropium Bromide

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 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
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
Period Title: Treatment Period 1
STARTED 56 13 13 12 12 11 12 14 12 13
COMPLETED 51 13 13 11 11 11 10 13 11 13
NOT COMPLETED 5 0 0 1 1 0 2 1 1 0
Period Title: Treatment Period 1
STARTED 53 13 10 13 13 10 10 13 11 11
COMPLETED 51 12 10 12 13 9 9 10 11 11
NOT COMPLETED 2 1 0 1 0 1 1 3 0 0
Period Title: Treatment Period 1
STARTED 51 12 10 12 13 9 9 10 11 11
COMPLETED 47 11 10 11 12 9 8 9 11 11
NOT COMPLETED 4 1 0 1 1 0 1 1 0 0
Period Title: Treatment Period 1
STARTED 46 9 10 11 12 9 12 10 9 11
COMPLETED 45 9 10 11 12 9 11 9 9 10
NOT COMPLETED 1 0 0 0 0 0 1 1 0 1

Baseline Characteristics

Arm/Group Title All Study Treatments
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 Participants 176
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
59.7
(8.12)
Sex: Female, Male (Count of Participants)
Female
75
42.6%
Male
101
57.4%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage
4
2.3%
White
172
97.7%

Outcome Measures

1. Primary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
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)

Outcome Measure Data

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
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.
Measure Participants 150 34 33 35 37 29 31 33 32 34
Least Squares Mean (Standard Error) [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)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 62.5 µg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.128
Confidence Interval (2-Sided) 95%
0.060 to 0.196
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 125 µg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.147
Confidence Interval (2-Sided) 95%
0.077 to 0.216
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 250 µg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.006
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.095
Confidence Interval (2-Sided) 95%
0.027 to 0.162
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 500 µg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.140
Confidence Interval (2-Sided) 95%
0.074 to 0.205
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 1000 µg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.186
Confidence Interval (2-Sided) 95%
0.113 to 0.259
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 62.5 µg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.030
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.079
Confidence Interval (2-Sided) 95%
0.008 to 0.151
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 125 µg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.134
Confidence Interval (2-Sided) 95%
0.064 to 0.204
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC 250 µg BID
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.172
Confidence Interval (2-Sided) 95%
0.101 to 0.242
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Tio 18 µg QD
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.003
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.105
Confidence Interval (2-Sided) 95%
0.037 to 0.173
Parameter Dispersion Type:
Value:
Estimation Comments
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
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)

Outcome Measure Data

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
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.
Measure Participants 143 33 33 34 36 29 30 32 31 33
Least Squares Mean (Standard Error) [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
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)

Outcome Measure Data

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
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.
Measure Participants 152 34 33 35 37 30 32 33 32 34
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)

Adverse Events

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
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/158 (0%) 0/35 (0%) 0/34 (0%) 2/36 (5.6%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 1/37 (2.7%) 0/33 (0%) 0/35 (0%)
Injury, poisoning and procedural complications
Concussion 0/158 (0%) 0/35 (0%) 0/34 (0%) 1/36 (2.8%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 0/158 (0%) 0/35 (0%) 0/34 (0%) 1/36 (2.8%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 1/37 (2.7%) 0/33 (0%) 0/35 (0%)
Other (Not Including 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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 11/158 (7%) 2/35 (5.7%) 3/34 (8.8%) 8/36 (22.2%) 9/38 (23.7%) 13/32 (40.6%) 4/34 (11.8%) 4/37 (10.8%) 10/33 (30.3%) 3/35 (8.6%)
Blood and lymphatic system disorders
Thrombocytosis 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 1/32 (3.1%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Gastrointestinal disorders
Dry mouth 1/158 (0.6%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 1/38 (2.6%) 2/32 (6.3%) 0/34 (0%) 1/37 (2.7%) 3/33 (9.1%) 1/35 (2.9%)
Nausea 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 0/32 (0%) 1/34 (2.9%) 0/37 (0%) 1/33 (3%) 0/35 (0%)
Infections and infestations
Nasopharyngitis 2/158 (1.3%) 0/35 (0%) 0/34 (0%) 2/36 (5.6%) 0/38 (0%) 4/32 (12.5%) 2/34 (5.9%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Cystitis 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 1/37 (2.7%) 1/33 (3%) 0/35 (0%)
Upper respiratory tract infection 1/158 (0.6%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 0/37 (0%) 1/33 (3%) 0/35 (0%)
Injury, poisoning and procedural complications
Joint sprain 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 0/37 (0%) 1/33 (3%) 0/35 (0%)
Investigations
Blood potassium increased 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 0/37 (0%) 1/33 (3%) 0/35 (0%)
Metabolism and nutrition disorders
Hyperkalaemia 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 1/32 (3.1%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 1/32 (3.1%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Pain in extremity 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 1/32 (3.1%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Nervous system disorders
Headache 4/158 (2.5%) 1/35 (2.9%) 1/34 (2.9%) 3/36 (8.3%) 1/38 (2.6%) 2/32 (6.3%) 0/34 (0%) 1/37 (2.7%) 3/33 (9.1%) 2/35 (5.7%)
Dysgeusia 0/158 (0%) 0/35 (0%) 0/34 (0%) 2/36 (5.6%) 0/38 (0%) 2/32 (6.3%) 1/34 (2.9%) 0/37 (0%) 2/33 (6.1%) 0/35 (0%)
Migraine 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 0/37 (0%) 1/33 (3%) 0/35 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 1/158 (0.6%) 1/35 (2.9%) 0/34 (0%) 1/36 (2.8%) 4/38 (10.5%) 2/32 (6.3%) 0/34 (0%) 0/37 (0%) 2/33 (6.1%) 0/35 (0%)
Oropharyngeal pain 2/158 (1.3%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 1/38 (2.6%) 0/32 (0%) 0/34 (0%) 1/37 (2.7%) 2/33 (6.1%) 0/35 (0%)
Dysphonia 1/158 (0.6%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 2/37 (5.4%) 0/33 (0%) 0/35 (0%)
Dyspnoea 1/158 (0.6%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 1/38 (2.6%) 1/32 (3.1%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Rhinitis allergic 1/158 (0.6%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 1/38 (2.6%) 1/32 (3.1%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Chronic obstructive pulmonary disease 0/158 (0%) 0/35 (0%) 0/34 (0%) 0/36 (0%) 0/38 (0%) 1/32 (3.1%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)
Vascular disorders
Hypertension 0/158 (0%) 0/35 (0%) 2/34 (5.9%) 1/36 (2.8%) 0/38 (0%) 0/32 (0%) 0/34 (0%) 0/37 (0%) 0/33 (0%) 0/35 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00950807
Other Study ID Numbers:
  • 113073
First Posted:
Aug 3, 2009
Last Update Posted:
Nov 8, 2017
Last Verified:
Oct 1, 2017