Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
COPD, Multicenter, GSK233705B, double-blind, Chronic Obstructive Pulmonary Disease (COPD), randomized
Brief summary
The purpose of this study is to evaluate the efficacy and safety of GSK233705B compared with placebo in subjects with COPD.
Interventions
DRUGGSK233705 200mcg
Once daily via dry powder inhaler
DRUGPlacebo
Once daily via dry powder imhaler
DRUGGSK233705 50mcg
Once daily via dry powder inhaler
DRUGGSK233705 12.5mcg
Once daily via dry powder inhaler
DRUGGSK233705 25mcg
once daily via dry powder inhaler
DRUGGSK233705 100mcg
Once daily via dry powder inhaler
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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. * Male or female adults. A female is eligible to enter and participate in this study if she is of: non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post-menopausal; or child-bearing potential, has a negative pregnancy test at Visit 1/Visit 1A, and agrees to one of the protocol-specified acceptable contraceptive methods used consistently and correctly (i.e. according to the approved product label and the instructions of the physician for the duration of the study - Screening through follow-up contact) * 40 to 80 years of age at Visit 1 * An established clinical history of COPD * Current or previous cigarette smokers with a history of cigarette smoking of ≥ 10 pack-years 1. * A post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 and a post-albuterol/salbutamol FEV1 of ≥35 and ≤70% of predicted normal values
Exclusion criteria
Subjects meeting any of the following criteria must not be enrolled in the study: * Women who are pregnant or lactating. * A current diagnosis of asthma. * Known respiratory disorders other than COPD including but not limited to α-1 antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease. * Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy) * Clinically significant Chest X-ray or computed tomography (CT) scan abnormalities within 6 months prior to Visit 1 that are not believed to be due to COPD. * Use of oral corticosteroids or antibiotics for COPD within 6 weeks prior to Visit 1. * Hospitalization for COPD or pneumonia within 3 months prior to Visit 1. * Use of antibiotics for a lower respiratory tract infection within 30 days prior to Visit 1. * Clinically significant and uncontrolled cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities. * An abnormal and clinically significant 12-lead electrocardiogram (ECG) that results in active medical problem. * Positive for Hepatitis B or Hepatitis C at Visit 1. * A current malignancy or previous history of cancer in remission for \<5 years prior to Visit 1 * A history of allergy or hypersensitivity to ipratropium, tiotropium, or atropine and any of their derivatives, lactose/milk protein or magnesium stearate. * Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholingeric. * Medically unable to withhold albuterol/salbutamol for 6 hours prior to spirometry testing at each study visit or to withhold ipratropium (if applicable) for the 6-hour period prior to the first 3 study visits (ipratropium cannot be used after Visit 3). * Additional Medications: Unable to stop using certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications) * Use of inhaled corticosteroids at a dose greater than 1000 mcg/day of fluticasone propionate or equivalent within 30 days prior to Visit 1. * Use of long-term oxygen therapy (LTOT) or supplemental oxygen required for greater than 12 hours a day. Oxygen use as needed is not exclusionary. * Clinically significant sleep apnea that requires continuous positive airway pressure (CPAP) * Use of regular nebulized therapy * Use of nocturnal positive pressure or non-invasive positive pressure ventilation (NIPPV) * Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. * An investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the above who is involved in this study * History of psychiatric disease, intellectual deficiency, poor motivation, substance abuse in the two years prior to Visit 1 (including drug and alcohol), or other conditions, which will limit the validity of informed consent to participate in the study. * Use of GSK233705B in previous studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | Baseline (pre-dose Day 1) and Day 29 | The trough FEV1 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. The Baseline FEV1 is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose \[time 0\] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29 | Weighted means serial FEV1 was derived by calculating the area under curve (AUC), and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used. |
| Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29 | Weighted means serial FVC was derived by calculating the AUC, and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used. |
| Change From Baseline in Clinic Visit Trough FVC on Day 29 | Baseline (pre-dose Day 1) and Day 29 | The trough FVC is defined as the mean of the FVC values obtained 23 and 24 hours after dosing on Day 28. The Baseline FVC is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose \[time 0\] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value. |
Countries
Argentina, Bulgaria, Canada, Chile, Germany, Hungary, Netherlands, Philippines, Romania, South Africa, South Korea, Thailand, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted across 79 centers: 30 in North America, 28 in Europe and 21 in International regions. The first participant first visit was on 16 May 2008 and last participant last visit was on 22 December 2008.
Pre-assignment details
Out of the 963 participants screened for this study, 303 participants were screen failures and 79 participants were run-in failures. Therefore, a total of 581 participants were randomized out of which 5 participants did not receive any study medication, thus 576 participants were included in the intent-to-treat (ITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive placebo administered once daily via a novel dry powder inhaler. | 96 |
| GSK233705B 12.5 mcg Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 12.5 mcg administered once daily via a novel dry powder inhaler. | 95 |
| GSK233705B 25 mcg Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 25 mcg administered once daily via a novel dry powder inhaler. | 96 |
| GSK233705B 50 mcg Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 50 mcg administered once daily via a novel dry powder inhaler. | 97 |
| GSK233705B 100 mcg Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 100 mcg administered once daily via a novel dry powder inhaler. | 95 |
| GSK233705B 200 mcg Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 200 mcg administered once daily via a novel dry powder inhaler. | 97 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 2 | 2 | 2 |
| Overall Study | Lack of Efficacy | 2 | 2 | 1 | 1 | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 3 | 2 | 2 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | GSK233705B 200 mcg | GSK233705B 100 mcg | GSK233705B 50 mcg | GSK233705B 25 mcg | GSK233705B 12.5 mcg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.4 Years STANDARD_DEVIATION 8.73 | 62.4 Years STANDARD_DEVIATION 8.58 | 64.1 Years STANDARD_DEVIATION 8.3 | 61.7 Years STANDARD_DEVIATION 8.77 | 62.8 Years STANDARD_DEVIATION 6.99 | 62.2 Years STANDARD_DEVIATION 8.7 | 62.2 Years STANDARD_DEVIATION 9.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 43 Participants | 9 Participants | 8 Participants | 7 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 16 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 84 Participants | 512 Participants | 85 Participants | 83 Participants | 88 Participants | 86 Participants | 86 Participants |
| Sex: Female, Male Female | 46 Participants | 235 Participants | 34 Participants | 33 Participants | 45 Participants | 43 Participants | 34 Participants |
| Sex: Female, Male Male | 50 Participants | 341 Participants | 63 Participants | 62 Participants | 52 Participants | 53 Participants | 61 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 95 | 0 / 96 | 0 / 97 | 0 / 95 | 1 / 97 |
| other Total, other adverse events | 7 / 96 | 4 / 95 | 6 / 96 | 9 / 97 | 5 / 95 | 3 / 97 |
| serious Total, serious adverse events | 0 / 96 | 0 / 95 | 2 / 96 | 1 / 97 | 1 / 95 | 1 / 97 |
Outcome results
Primary
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29
The trough FEV1 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. The Baseline FEV1 is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose \[time 0\] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.
Time frame: Baseline (pre-dose Day 1) and Day 29
Population: ITT Population. Last observation carried forward (LOCF) data has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GSK233705B 12.5 mcg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | 0.058 Liter | Standard Error 0.018 |
| GSK233705B 25 mcg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | 0.088 Liter | Standard Error 0.018 |
| GSK233705B 50 mcg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | 0.060 Liter | Standard Error 0.0178 |
| GSK233705B 100 mcg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | 0.073 Liter | Standard Error 0.0181 |
| GSK233705B 200 mcg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | 0.128 Liter | Standard Error 0.0179 |
| Placebo | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | -0.009 Liter | Standard Error 0.0181 |
p-value: 0.00995% CI: [0.017, 0.117]ANCOVA
p-value: <0.00195% CI: [0.047, 0.147]ANCOVA
p-value: 0.00795% CI: [0.019, 0.118]ANCOVA
p-value: 0.00195% CI: [0.032, 0.132]ANCOVA
p-value: <0.00195% CI: [0.086, 0.187]ANCOVA
Secondary
Change From Baseline in Clinic Visit Trough FVC on Day 29
The trough FVC is defined as the mean of the FVC values obtained 23 and 24 hours after dosing on Day 28. The Baseline FVC is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose \[time 0\] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.
Time frame: Baseline (pre-dose Day 1) and Day 29
Population: ITT Population. Participants with analyzable data on the indicated time point have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GSK233705B 12.5 mcg | Change From Baseline in Clinic Visit Trough FVC on Day 29 | 0.088 Liter | Standard Error 0.0301 |
| GSK233705B 25 mcg | Change From Baseline in Clinic Visit Trough FVC on Day 29 | 0.139 Liter | Standard Error 0.0298 |
| GSK233705B 50 mcg | Change From Baseline in Clinic Visit Trough FVC on Day 29 | 0.083 Liter | Standard Error 0.0295 |
| GSK233705B 100 mcg | Change From Baseline in Clinic Visit Trough FVC on Day 29 | 0.152 Liter | Standard Error 0.03 |
| GSK233705B 200 mcg | Change From Baseline in Clinic Visit Trough FVC on Day 29 | 0.224 Liter | Standard Error 0.0297 |
| Placebo | Change From Baseline in Clinic Visit Trough FVC on Day 29 | -0.011 Liter | Standard Error 0.0301 |
p-value: 0.02195% CI: [0.015, 0.182]Repeated Measures Model
p-value: <0.00195% CI: [0.067, 0.233]Repeated Measures Model
p-value: 0.02695% CI: [0.011, 0.177]Repeated Measures Model
p-value: <0.00195% CI: [0.08, 0.247]Repeated Measures Model
p-value: <0.00195% CI: [0.152, 0.319]Repeated Measures Model
Secondary
Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29
Weighted means serial FVC was derived by calculating the AUC, and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used.
Time frame: Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29
Population: ITT Population. Participants with analyzable data on the indicated time point have been presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK233705B 12.5 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 1 | 0.129 Liter | Standard Error 0.0257 |
| GSK233705B 12.5 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 28 | 0.137 Liter | Standard Error 0.0287 |
| GSK233705B 25 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 1 | 0.149 Liter | Standard Error 0.0257 |
| GSK233705B 25 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 28 | 0.178 Liter | Standard Error 0.0285 |
| GSK233705B 50 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 1 | 0.160 Liter | Standard Error 0.0253 |
| GSK233705B 50 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 28 | 0.150 Liter | Standard Error 0.0283 |
| GSK233705B 100 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 1 | 0.207 Liter | Standard Error 0.0257 |
| GSK233705B 100 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 28 | 0.191 Liter | Standard Error 0.0287 |
| GSK233705B 200 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 1 | 0.263 Liter | Standard Error 0.0257 |
| GSK233705B 200 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 28 | 0.253 Liter | Standard Error 0.0283 |
| Placebo | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 1 | -0.037 Liter | Standard Error 0.0257 |
| Placebo | Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29 | Day 28 | -0.041 Liter | Standard Error 0.0289 |
Comparison: Day 1p-value: <0.00195% CI: [0.094, 0.237]Repeated Measures Model
Comparison: Day 1p-value: <0.00195% CI: [0.115, 0.258]Repeated Measures Model
Comparison: Day 1p-value: <0.00195% CI: [0.127, 0.268]Repeated Measures Model
Comparison: Day 1p-value: <0.00195% CI: [0.172, 0.315]Repeated Measures Model
Comparison: Day 1p-value: <0.00195% CI: [0.229, 0.372]Repeated Measures Model
Comparison: Day 28p-value: <0.00195% CI: [0.098, 0.258]Repeated Measures Model
Comparison: Day 28p-value: <0.00195% CI: [0.139, 0.298]Repeated Measures Model
Comparison: Day 28p-value: <0.00195% CI: [0.111, 0.27]Repeated Measures Model
Comparison: Day 28p-value: <0.00195% CI: [0.152, 0.312]Repeated Measures Model
Comparison: Day 28p-value: <0.00195% CI: [0.214, 0.373]Repeated Measures Model
Secondary
Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29
Weighted means serial FEV1 was derived by calculating the area under curve (AUC), and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used.
Time frame: Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29
Population: ITT Population. Participants with analyzable data on the indicated time point have been presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK233705B 12.5 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 1 | 0.085 Liter | Standard Error 0.0146 |
| GSK233705B 12.5 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 28 | 0.087 Liter | Standard Error 0.018 |
| GSK233705B 25 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 28 | 0.122 Liter | Standard Error 0.0179 |
| GSK233705B 25 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 1 | 0.086 Liter | Standard Error 0.0146 |
| GSK233705B 50 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 1 | 0.102 Liter | Standard Error 0.0143 |
| GSK233705B 50 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 28 | 0.105 Liter | Standard Error 0.0178 |
| GSK233705B 100 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 1 | 0.132 Liter | Standard Error 0.0146 |
| GSK233705B 100 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 28 | 0.122 Liter | Standard Error 0.018 |
| GSK233705B 200 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 1 | 0.155 Liter | Standard Error 0.0144 |
| GSK233705B 200 mcg | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 28 | 0.150 Liter | Standard Error 0.0178 |
| Placebo | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 28 | -0.020 Liter | Standard Error 0.0182 |
| Placebo | Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29 | FEV1, Day 1 | -0.021 Liter | Standard Error 0.0146 |
Comparison: FEV1, Day 1p-value: <0.00195% CI: [0.083, 0.163]Repeated Measures Model
Comparison: FEV1, Day 1p-value: <0.00195% CI: [0.112, 0.193]Repeated Measures Model
Comparison: FEV1, Day 1p-value: <0.00195% CI: [0.065, 0.146]Repeated Measures Model
Comparison: FEV1, Day 1p-value: <0.00195% CI: [0.067, 0.147]Repeated Measures Model
Comparison: FEV1, Day 1p-value: <0.00195% CI: [0.135, 0.216]Repeated Measures Model
Comparison: FEV1, Day 28p-value: <0.00195% CI: [0.056, 0.157]Repeated Measures Model
Comparison: FEV, Day 28p-value: <0.00195% CI: [0.092, 0.192]Repeated Measures Model
Comparison: FEV1, Day 28p-value: <0.00195% CI: [0.074, 0.174]Repeated Measures Model
Comparison: FEV1, Day 28p-value: <0.00195% CI: [0.092, 0.193]Repeated Measures Model
Comparison: FEV1, Day 28p-value: <0.00195% CI: [0.12, 0.22]Repeated Measures Model