Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Dose ranging, Chronic Bronchitis, Long-acting muscarinic antagonist, cross-over, COPD, Emphysema, Chronic Obstructive Pulmonary Disease (COPD), anticholinergic
Brief summary
The study will evaluate the dose response, safety, and pharmacokinetics of GSK573719 compared with placebo in subjects with COPD.
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.
Interventions
DRUGTiotropium
long-acting muscarinic receptor antagonist; 18mcg once-daily
DRUGPlacebo
Inactive/ excipients only
DRUGGSK573179
GSK573179 investigational drug
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
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 C) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Germany, United States
Participant flow
Pre-assignment details
Participants (par.) who were eligible completed a 4- to 7-day Run-in period prior to randomization. The treatment (trt) phase was comprised of three 14-day trt periods. Par. were randomly assigned to receive a sequence of placebo and 2 of the 9 active trts over the trt phase. Participant Flow data are presented by treatment rather than sequence.
Participants by arm
| Arm | Count |
|---|---|
| All Study Treatments 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. | 176 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 2 | Adverse Event | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 |
| Treatment Period 2 | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 | Protocol-defined Stopping Criteria | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 |
| Treatment Period 3 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 3 | Protocol-defined Stopping Criteria | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Period 1 | Adverse Event | 2 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout Period 1 | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Washout Period 1 | Protocol-defined Stopping Criteria | 3 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Washout Period 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Washout Period 2 | Adverse Event | 3 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Washout Period 2 | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Washout Period 2 | Protocol-defined Stopping Criteria | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Study Treatments |
|---|---|
| Age, Continuous | 59.7 Years STANDARD_DEVIATION 8.12 |
| Race/Ethnicity, Customized African American/African Heritage | 4 Participants |
| Race/Ethnicity, Customized White | 172 Participants |
| Sex: Female, Male Female | 75 Participants |
| Sex: Female, Male Male | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 158 | 2 / 35 | 3 / 34 | 8 / 36 | 9 / 38 | 13 / 32 | 4 / 34 | 4 / 37 | 10 / 33 | 3 / 35 |
| serious Total, serious adverse events | 0 / 158 | 0 / 35 | 0 / 34 | 2 / 36 | 0 / 38 | 0 / 32 | 0 / 34 | 1 / 37 | 0 / 33 | 0 / 35 |
Outcome results
Primary
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
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)
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | -0.047 Liters | Standard Error 0.017 |
| UMEC 62.5 µg QD | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.081 Liters | Standard Error 0.033 |
| UMEC 125 µg QD | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.099 Liters | Standard Error 0.034 |
| UMEC 250 µg QD | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.048 Liters | Standard Error 0.033 |
| UMEC 500 µg QD | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.092 Liters | Standard Error 0.032 |
| UMEC 1000 µg QD | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.138 Liters | Standard Error 0.036 |
| UMEC 62.5 µg BID | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.032 Liters | Standard Error 0.035 |
| UMEC 125 µg BID | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.087 Liters | Standard Error 0.034 |
| UMEC 250 µg BID | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.124 Liters | Standard Error 0.034 |
| Tio 18 µg QD | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period | 0.058 Liters | Standard Error 0.033 |
p-value: <0.00195% CI: [0.06, 0.196]Mixed Models Analysis
p-value: <0.00195% CI: [0.077, 0.216]Mixed Models Analysis
p-value: 0.00695% CI: [0.027, 0.162]Mixed Models Analysis
p-value: <0.00195% CI: [0.074, 0.205]Mixed Models Analysis
p-value: <0.00195% CI: [0.113, 0.259]Mixed Models Analysis
p-value: 0.0395% CI: [0.008, 0.151]Mixed Models Analysis
p-value: <0.00195% CI: [0.064, 0.204]Mixed Models Analysis
p-value: <0.00195% CI: [0.101, 0.242]Mixed Models Analysis
p-value: 0.00395% CI: [0.037, 0.173]Mixed Models Analysis
Secondary
Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | -0.082 Liters | Standard Deviation 0.016 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | -0.019 Liters | Standard Deviation 0.016 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | -0.051 Liters | Standard Deviation 0.017 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | -0.003 Liters | Standard Deviation 0.017 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.065 Liters | Standard Deviation 0.018 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | -0.033 Liters | Standard Deviation 0.016 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | -0.002 Liters | Standard Deviation 0.016 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | -0.085 Liters | Standard Deviation 0.016 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | -0.147 Liters | Standard Deviation 0.017 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | -0.068 Liters | Standard Deviation 0.018 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.022 Liters | Standard Deviation 0.018 |
| Placebo | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | -0.145 Liters | Standard Deviation 0.016 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | 0.009 Liters | Standard Deviation 0.034 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.071 Liters | Standard Deviation 0.031 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.074 Liters | Standard Deviation 0.031 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.179 Liters | Standard Deviation 0.035 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.246 Liters | Standard Deviation 0.035 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.157 Liters | Standard Deviation 0.034 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.067 Liters | Standard Deviation 0.033 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.137 Liters | Standard Deviation 0.031 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.121 Liters | Standard Deviation 0.033 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.140 Liters | Standard Deviation 0.031 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | -0.053 Liters | Standard Deviation 0.033 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.087 Liters | Standard Deviation 0.035 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | 0.035 Liters | Standard Deviation 0.034 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.164 Liters | Standard Deviation 0.037 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.177 Liters | Standard Deviation 0.036 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.077 Liters | Standard Deviation 0.033 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.158 Liters | Standard Deviation 0.035 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.077 Liters | Standard Deviation 0.031 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.101 Liters | Standard Deviation 0.032 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.083 Liters | Standard Deviation 0.036 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.114 Liters | Standard Deviation 0.032 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.093 Liters | Standard Deviation 0.034 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.051 Liters | Standard Deviation 0.032 |
| UMEC 125 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | 0.002 Liters | Standard Deviation 0.033 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.222 Liters | Standard Deviation 0.034 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.167 Liters | Standard Deviation 0.031 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | -0.036 Liters | Standard Deviation 0.034 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.140 Liters | Standard Deviation 0.035 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.149 Liters | Standard Deviation 0.031 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.212 Liters | Standard Deviation 0.035 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.123 Liters | Standard Deviation 0.032 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | -0.018 Liters | Standard Deviation 0.032 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.069 Liters | Standard Deviation 0.031 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.071 Liters | Standard Deviation 0.031 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.045 Liters | Standard Deviation 0.033 |
| UMEC 250 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.084 Liters | Standard Deviation 0.035 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.056 Liters | Standard Deviation 0.034 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.103 Liters | Standard Deviation 0.03 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.142 Liters | Standard Deviation 0.033 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.120 Liters | Standard Deviation 0.03 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.143 Liters | Standard Deviation 0.034 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.088 Liters | Standard Deviation 0.032 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | -0.007 Liters | Standard Deviation 0.031 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.096 Liters | Standard Deviation 0.034 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.118 Liters | Standard Deviation 0.031 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.038 Liters | Standard Deviation 0.03 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | 0.004 Liters | Standard Deviation 0.033 |
| UMEC 500 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.095 Liters | Standard Deviation 0.03 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.050 Liters | Standard Deviation 0.033 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.120 Liters | Standard Deviation 0.033 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.072 Liters | Standard Deviation 0.038 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.148 Liters | Standard Deviation 0.037 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.105 Liters | Standard Deviation 0.034 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.076 Liters | Standard Deviation 0.035 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.074 Liters | Standard Deviation 0.038 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.096 Liters | Standard Deviation 0.033 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | 0.001 Liters | Standard Deviation 0.035 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | 0.006 Liters | Standard Deviation 0.037 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.142 Liters | Standard Deviation 0.036 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.191 Liters | Standard Deviation 0.038 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | -0.059 Liters | Standard Deviation 0.036 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.021 Liters | Standard Deviation 0.035 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.153 Liters | Standard Deviation 0.036 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.066 Liters | Standard Deviation 0.032 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.058 Liters | Standard Deviation 0.037 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.105 Liters | Standard Deviation 0.034 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.096 Liters | Standard Deviation 0.032 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.164 Liters | Standard Deviation 0.037 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | -0.020 Liters | Standard Deviation 0.034 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.085 Liters | Standard Deviation 0.033 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.159 Liters | Standard Deviation 0.037 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.090 Liters | Standard Deviation 0.033 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.054 Liters | Standard Deviation 0.032 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | 0.029 Liters | Standard Deviation 0.035 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.099 Liters | Standard Deviation 0.036 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.100 Liters | Standard Deviation 0.032 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.112 Liters | Standard Deviation 0.035 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.219 Liters | Standard Deviation 0.036 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.132 Liters | Standard Deviation 0.036 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | 0.016 Liters | Standard Deviation 0.033 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.018 Liters | Standard Deviation 0.032 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.091 Liters | Standard Deviation 0.034 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.104 Liters | Standard Deviation 0.033 |
| UMEC 125 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.139 Liters | Standard Deviation 0.032 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.141 Liters | Standard Deviation 0.033 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.074 Liters | Standard Deviation 0.036 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.096 Liters | Standard Deviation 0.032 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.099 Liters | Standard Deviation 0.034 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | -0.048 Liters | Standard Deviation 0.033 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.153 Liters | Standard Deviation 0.036 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | -0.005 Liters | Standard Deviation 0.035 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.142 Liters | Standard Deviation 0.037 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.185 Liters | Standard Deviation 0.037 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.139 Liters | Standard Deviation 0.035 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.152 Liters | Standard Deviation 0.032 |
| UMEC 250 µg BID | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.048 Liters | Standard Deviation 0.032 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 13 hour AM, n=147,33,33,35,37,29,31,33,32,33 | 0.065 Liters | Standard Deviation 0.031 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 24 hour AM, n=150,34,33,35,37,29,31,33,32,34 | 0.047 Liters | Standard Deviation 0.033 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 12 hour AM, n=150,34,33,34,37,30,31,32,32,33 | 0.153 Liters | Standard Deviation 0.036 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | Pre-AM dose, n=152,34,33,35,37,30,32,33,32,34 | 0.129 Liters | Standard Deviation 0.031 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 9 hour AM, n=149,33,33,34,37,30,31,32,32,33 | 0.105 Liters | Standard Deviation 0.033 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 18 hour AM, n=148,33,33,35,36,29,31,33,32,34 | -0.097 Liters | Standard Deviation 0.032 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 6 hour AM, n=151,34,33,35,37,30,32,33,31,34 | 0.152 Liters | Standard Deviation 0.032 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 28 hour AM, n=145,34,33,35,37,29,31,33,32,34 | 0.108 Liters | Standard Deviation 0.035 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 1 hour AM, n=151,34,31,35,37,29,32,33,32,34 | 0.229 Liters | Standard Deviation 0.036 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 15 hour AM, n=151,34,33,35,37,29,30,33,32,34 | 0.036 Liters | Standard Deviation 0.031 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 21 hour AM, n=150,34,33,35,37,29,29,33,32,34 | -0.060 Liters | Standard Deviation 0.034 |
| Tio 18 µg QD | Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period | 3 hour AM, n=150,34,32,35,37,29,31,33,32,34 | 0.191 Liters | Standard Deviation 0.035 |
Secondary
Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period
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)
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | -0.059 Liters | Standard Error 0.014 |
| UMEC 62.5 µg QD | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.085 Liters | Standard Error 0.025 |
| UMEC 125 µg QD | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.077 Liters | Standard Error 0.025 |
| UMEC 250 µg QD | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.077 Liters | Standard Error 0.025 |
| UMEC 500 µg QD | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.072 Liters | Standard Error 0.024 |
| UMEC 1000 µg QD | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.080 Liters | Standard Error 0.027 |
| UMEC 62.5 µg BID | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.062 Liters | Standard Error 0.026 |
| UMEC 125 µg BID | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.083 Liters | Standard Error 0.025 |
| UMEC 250 µg BID | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.075 Liters | Standard Error 0.026 |
| Tio 18 µg QD | Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period | 0.069 Liters | Standard Error 0.025 |