Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
chronic obstructive pulmonary disease, long acting muscarinic antagonist
Brief summary
The purpose of this study is to assess if 12 weeks' treatment with GSK573719 Inhalation Powder is safe and effective compared with placebo or no active drug intake, when administered once-daily in subjects with Chronic Obstructive Pulmonary Disease (COPD).
Detailed description
Inhaled bronchodilators, such as beta 2 agonists and anticholinergics, and inhaled corticosteroids are the mainstays of therapy in patients diagnosed with COPD. Anticholinergic bronchodilators or long acting muscarinic receptor antagonists function by blocking endogenous airway smooth muscle cholinergic tone. Treatment with anticholinergics has been shown to significantly improve forced expiratory volume in 1 second (FEV1), resting and dynamic lung hyperinflation, symptoms, and exercise capacity in patients with COPD. Currently tiotropium is the only approved long acting muscarinic antagonist available for treatment of COPD.This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder of 2 doses when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD. There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. There will be 8 clinic visits during three of which serial spirometry will be performed . The total duration of subject participation in the study will be approximately 14 weeks. This is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder 62.5 mcg and 125 mcg when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD. Eligible subjects will be randomized 1:1:1 to receive either of the two doses of GSK573719 Inhalation Powder doses or placebo for 12 weeks. There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. Clinic visits will be at Screening, Randomization (Visit 2), Day 3 and Weeks 2, 4, 8, and 12, and 1 day after the Week 12 visit (Visits 1 to 8, respectively). A safety follow-up assessment will be conducted by telephone approximately 7 days after the end of the study treatment (FU Phone Contact). The total duration of subject participation, including the follow-up period will be approximately 14 weeks. All subjects will be provided with albuterol/salbutamol for use on an as-needed basis throughout the run-in and treatment periods. Pre-dose spirometry will be conducted at each clinic visit. Six hour post-dose serial spirometry will be conducted at Visit 2 and at Visits 5 and 7. All subjects will be provided with a paper diary for completion everyday throughout the run-in period and 12-week treatment period. Subjects will use the diary to record their daily use of supplemental albuterol/salbutamol and to record any medical problems experienced and any medications used. At Visit 2 the Baseline Dyspnea Index (BDI) will be administered. The Transition Dyspnea Index (TDI) will be administered at Visits 5, 6, and 7. Disease specific health status will be evaluated using the St. George's Respiratory Questionnaire (SGRQ) at Visit 2 and Visits 5, 6 and 7. Vital signs (blood pressure and pulse rate), 12-lead ECGs and standard clinical laboratory tests (hematology and blood biochemistry) including pharmacokinetic samples will be obtained at selected clinic visits. Approximately 198 subjects will be randomized to ensure at least 168 subjects complete the treatment period.
Interventions
DRUGGSK573719
62.5 mcg
OTHERPlacebo
Placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of COPD * 10 pack-year or greater history of cigarette smoking * Post-bronchodilator FEV1/FVC of \<0.7 * Predicted FEV1 of 70% of normal or less * Modified Medical Research Council (mMRC) dyspnea score of 2 or greater
Exclusion criteria
* Women who are pregnant, lactating, or planning to become pregnant * Respiratory disorders other than COPD, including a current diagnosis of asthma * Clinically significant non-respiratory diseases or abnormalities that are not adequately controlled * Significant allergy or hypersensitivity to anticholinergics, beta2-agonists, or the excipients of magnesium stereate or lactose used in the inhaler delivery device * Hospitalization for COPD or pneumonia within 12 weeks prior to screening * Lung volume reduction surgery within 12 weeks prior to screening * Abnormal and clinically significant ECG findings at screening * Clinically significant laboratory findings at screening * Use of systemic corticosteroids, antibiotics for respiratory tract infections, high dose inhaled steroids (\>1000mcg fluticasone propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled beta2-agonists, inhaled sodium cromoglycate or nedocromil sodium, or investigational medicines for defined time periods prior to the screening visit * Use of long-term oxygen therapy (12 hours or greater per day) * Regular use of nebulized treatment with short-acting bronchodilators * Participation in the acute phase of a pulmonary rehabilitation program * A know or suspected history of alcohol or drug abuse * Affiliation with the investigational site * Previous use of GSK573719 or the combination of GSK573719/GW642444
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 | Baseline and Day 85 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 14, 28, 56, 84, and 85. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 85 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 84). Change from Baseline was calculated as the trough FEV1 minus the Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Baseline and Days 1, 28 and 84 | 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 WM 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 WM was calculated at Days 1, 28, and Day 84 using the 0-6-hour post-dose FEV1 measurements collected on that day, which included pre-dose (Day 1: 30 minutes \[min\] and 5 min prior to dosing; other serial visits: 23 and 24 hours after the previous morning dose) and post-dose at 1 hour, 3 hours, and 6 hours. Change from Baseline was the WM minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, center group, day, and day by Baseline and day by treatment interactions. |
| Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Baseline, Day 1 and Day 84 | Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 measurements of interest for Day 1 were collected at 1, 3, 6, 23 and 24 hours post-dose on Day 1 and for Day 84, the measures were pre-dose (24 hours post-dose of Day 83 morning dose but prior to Day 84's dose) and 1, 3, 6, 23 and 24 hours post dose on Day 84. Baseline is the mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis performed separately by Visit/Day using a repeated measures model with covariates of treatment, Baseline, smoking status, center group, time, time by Baseline and time by treatment interactions. |
Countries
Germany, Japan, United States
Participant flow
Pre-assignment details
Participants (par.) who met eligibility criteria at Screening (Visit 1) completed a 5- to 9-day run-in period and were then randomized to a 12-week treatment period. A total of 246 par. were screened; 206 par. who were eligible were randomized and 206 par. received at least one dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo QD via a DPI in the morning for 12 weeks. | 68 |
| UMEC 62.5 µg Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks. | 69 |
| UMEC 125 µg Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks. | 69 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 3 |
| Overall Study | Lack of Efficacy | 8 | 5 | 4 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol-defined Stopping Criteria | 6 | 0 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | UMEC 62.5 µg | UMEC 125 µg | Total |
|---|---|---|---|---|
| Age, Continuous | 62.5 Years STANDARD_DEVIATION 8.72 | 62.3 Years STANDARD_DEVIATION 9.5 | 64.6 Years STANDARD_DEVIATION 7.96 | 63.1 Years STANDARD_DEVIATION 8.77 |
| Race/Ethnicity, Customized African American/African Heritage | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 8 Participants | 7 Participants | 6 Participants | 21 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 58 Participants | 60 Participants | 61 Participants | 179 Participants |
| Sex: Female, Male Female | 26 Participants | 25 Participants | 27 Participants | 78 Participants |
| Sex: Female, Male Male | 42 Participants | 44 Participants | 42 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 68 | 12 / 69 | 19 / 69 |
| serious Total, serious adverse events | 1 / 68 | 1 / 69 | 2 / 69 |
Outcome results
Primary
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 14, 28, 56, 84, and 85. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 85 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 84). Change from Baseline was calculated as the trough FEV1 minus the Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions.
Time frame: Baseline and Day 85
Population: Intent-to-Treat (ITT) Population: all randomized par. who received \>=1 dose of study drug. Par. analyzed are those with data available at the presented time point; but, all par. without missing covariate information and with \>=1 post-BL measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 | -0.007 Liters | Standard Error 0.028 |
| UMEC 62.5 µg | Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 | 0.120 Liters | Standard Error 0.0257 |
| UMEC 125 µg | Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 | 0.145 Liters | Standard Error 0.0268 |
p-value: <0.00195% CI: [0.052, 0.202]Mixed Models Analysis
p-value: <0.00195% CI: [0.076, 0.229]Mixed Models Analysis
Secondary
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12)
Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 measurements of interest for Day 1 were collected at 1, 3, 6, 23 and 24 hours post-dose on Day 1 and for Day 84, the measures were pre-dose (24 hours post-dose of Day 83 morning dose but prior to Day 84's dose) and 1, 3, 6, 23 and 24 hours post dose on Day 84. Baseline is the mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis performed separately by Visit/Day using a repeated measures model with covariates of treatment, Baseline, smoking status, center group, time, time by Baseline and time by treatment interactions.
Time frame: Baseline, Day 1 and Day 84
Population: ITT Population. All participants with \>=1 post-BL assessment and non-missing covariate data are included in the analysis. Different participants may have been analyzed at different time points (represented by n=X, X, X in the category titles), so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 1 hour, n=68, 69, 69 | -0.001 Liters | Standard Error 0.0148 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 3 hours ,n=68, 69, 69 | 0.035 Liters | Standard Error 0.0187 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 23 hours, n=67, 69, 65 | -0.027 Liters | Standard Error 0.0178 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 24 hours, n=67, 69, 66 | -0.020 Liters | Standard Error 0.019 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 1 hour,n=50, 60, 56 | -0.025 Liters | Standard Error 0.0299 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 23 hours, n=50, 60, 55 | -0.019 Liters | Standard Error 0.0301 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 24 hours, n=50, 61, 55 | 0.020 Liters | Standard Error 0.0299 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 6 hours, n=66, 69, 69 | 0.000 Liters | Standard Error 0.0206 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, Pre-dose, n=50, 60, 56 | 0.002 Liters | Standard Error 0.0299 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 3 hours, n=50, 61, 56 | 0.012 Liters | Standard Error 0.0301 |
| Placebo | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 6 hours,n=49, 61, 56 | 0.006 Liters | Standard Error 0.0286 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 1 hour,n=50, 60, 56 | 0.167 Liters | Standard Error 0.027 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 23 hours, n=50, 60, 55 | 0.106 Liters | Standard Error 0.0271 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 6 hours,n=49, 61, 56 | 0.159 Liters | Standard Error 0.0257 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 24 hours, n=50, 61, 55 | 0.142 Liters | Standard Error 0.0269 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 3 hours ,n=68, 69, 69 | 0.165 Liters | Standard Error 0.0186 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 3 hours, n=50, 61, 56 | 0.189 Liters | Standard Error 0.0271 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 6 hours, n=66, 69, 69 | 0.156 Liters | Standard Error 0.0203 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 1 hour, n=68, 69, 69 | 0.132 Liters | Standard Error 0.0147 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 24 hours, n=67, 69, 66 | 0.099 Liters | Standard Error 0.0188 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 23 hours, n=67, 69, 65 | 0.070 Liters | Standard Error 0.0176 |
| UMEC 62.5 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, Pre-dose, n=50, 60, 56 | 0.155 Liters | Standard Error 0.0269 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 23 hours, n=67, 69, 65 | 0.113 Liters | Standard Error 0.018 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 6 hours,n=49, 61, 56 | 0.178 Liters | Standard Error 0.027 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 1 hour,n=50, 60, 56 | 0.199 Liters | Standard Error 0.0283 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, Pre-dose, n=50, 60, 56 | 0.177 Liters | Standard Error 0.0283 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 23 hours, n=50, 60, 55 | 0.142 Liters | Standard Error 0.0286 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 1 hour, n=68, 69, 69 | 0.142 Liters | Standard Error 0.0147 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 3 hours, n=50, 61, 56 | 0.219 Liters | Standard Error 0.0285 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 84, 24 hours, n=50, 61, 55 | 0.170 Liters | Standard Error 0.0284 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 3 hours ,n=68, 69, 69 | 0.210 Liters | Standard Error 0.0186 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 6 hours, n=66, 69, 69 | 0.169 Liters | Standard Error 0.0203 |
| UMEC 125 µg | Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) | Day 1, 24 hours, n=67, 69, 66 | 0.151 Liters | Standard Error 0.0191 |
Secondary
Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12)
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 WM 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 WM was calculated at Days 1, 28, and Day 84 using the 0-6-hour post-dose FEV1 measurements collected on that day, which included pre-dose (Day 1: 30 minutes \[min\] and 5 min prior to dosing; other serial visits: 23 and 24 hours after the previous morning dose) and post-dose at 1 hour, 3 hours, and 6 hours. Change from Baseline was the WM minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, center group, day, and day by Baseline and day by treatment interactions.
Time frame: Baseline and Days 1, 28 and 84
Population: ITT Population. All participants with \>=1 post-BL assessment and non-missing covariate data are included in the analysis. Different participants may have been analyzed at different time points (represented by n=X, X, X in the category titles), so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 28, n= 53, 65, 60 | -0.024 Liters | Standard Error 0.0223 |
| Placebo | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 1, n=66, 69, 69 | 0.017 Liters | Standard Error 0.015 |
| Placebo | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 84, n= 49, 60, 56 | -0.003 Liters | Standard Error 0.0271 |
| UMEC 62.5 µg | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 84, n= 49, 60, 56 | 0.163 Liters | Standard Error 0.0248 |
| UMEC 62.5 µg | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 28, n= 53, 65, 60 | 0.141 Liters | Standard Error 0.0206 |
| UMEC 62.5 µg | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 1, n=66, 69, 69 | 0.141 Liters | Standard Error 0.0147 |
| UMEC 125 µg | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 84, n= 49, 60, 56 | 0.188 Liters | Standard Error 0.0256 |
| UMEC 125 µg | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 1, n=66, 69, 69 | 0.164 Liters | Standard Error 0.0147 |
| UMEC 125 µg | Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) | Day 28, n= 53, 65, 60 | 0.172 Liters | Standard Error 0.0212 |