Trial Outcomes & Findings for 1-year Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00929110)
NCT ID: NCT00929110
Last Updated: 2012-08-17
Results Overview
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose. The analysis included baseline FEV1 measurement, baseline inhaled corticosteroid use (Yes/No), FEV1 prior to inhalation of short-acting β2 agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1066 participants
Primary outcome timeframe
Week 12
Results posted on
2012-08-17
Participant Flow
A total of 1993 patients were screened from 180 participating sites, of whom 1066 were randomized to 1 of the 3 treatment groups in a 2:1:1 ratio glycopyrronium bromide:placebo:tiotropium.
Participant milestones
| Measure |
Glycopyrronium Bromide 50 μg
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
529
|
269
|
268
|
|
Overall Study
COMPLETED
|
411
|
193
|
206
|
|
Overall Study
NOT COMPLETED
|
118
|
76
|
62
|
Reasons for withdrawal
| Measure |
Glycopyrronium Bromide 50 μg
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
40
|
29
|
18
|
|
Overall Study
Subject withdrew consent
|
40
|
23
|
26
|
|
Overall Study
Unsatisfactory therapeutic effect
|
20
|
9
|
6
|
|
Overall Study
Lost to Follow-up
|
7
|
7
|
3
|
|
Overall Study
Protocol deviation
|
5
|
2
|
4
|
|
Overall Study
Administrative problems
|
4
|
1
|
2
|
|
Overall Study
Death
|
2
|
2
|
2
|
|
Overall Study
Abnormal laboratory value(s)
|
0
|
1
|
0
|
|
Overall Study
Abnormal test procedure result(s)
|
0
|
1
|
1
|
|
Overall Study
Patient inability to use the device
|
0
|
1
|
0
|
Baseline Characteristics
1-year Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
Glycopyrronium Bromide 50 μg
n=525 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=268 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=267 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Total
n=1060 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
63.5 years
STANDARD_DEVIATION 9.05 • n=5 Participants
|
63.6 years
STANDARD_DEVIATION 9.14 • n=7 Participants
|
63.9 years
STANDARD_DEVIATION 8.25 • n=5 Participants
|
63.6 years
STANDARD_DEVIATION 8.87 • n=4 Participants
|
|
Sex: Female, Male
Female
|
186 Participants
n=5 Participants
|
95 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
380 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
339 Participants
n=5 Participants
|
173 Participants
n=7 Participants
|
168 Participants
n=5 Participants
|
680 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose. The analysis included baseline FEV1 measurement, baseline inhaled corticosteroid use (Yes/No), FEV1 prior to inhalation of short-acting β2 agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=513 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=245 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=253 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
|
1.469 Liters
Standard Error 0.0141
|
1.372 Liters
Standard Error 0.0173
|
1.455 Liters
Standard Error 0.0170
|
SECONDARY outcome
Timeframe: Week 26Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
The TDI measured changes in dyspnea from baseline during treatment and included 3 domains: Functional impairment (activities of daily living), magnitude of task (intensity of activity), and magnitude of effort (difficulty breathing). Each domain was rated from -3 to 3 (major deterioration-major improvement). The total score ranged from -9 to 9; minus scores indicate deterioration. The analysis included the same covariates as the primary Outcome Measure.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=470 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=217 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=238 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Transition Dyspnea Index (TDI) at Week 26
|
2.13 Units on a scale
Standard Error 0.240
|
1.32 Units on a scale
Standard Error 0.289
|
2.26 Units on a scale
Standard Error 0.281
|
SECONDARY outcome
Timeframe: Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
The SGRQ contained 51 patient-rated items divided into three components: Symptoms (respiratory symptoms, their frequency, and severity), Activity (activities that cause or are limited by breathlessness), and Impacts (social functioning and psychological disturbances resulting from airway disease). A total score for the 3 components was calculated and ranged from 0 to 100. Higher values indicate greater impairment of QoL. The analysis included the same covariates as the primary Outcome Measure.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=499 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=248 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=251 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Health-related Quality of Life (QoL) Assessed With the St. George Respiratory Questionnaire (SGRQ) at Week 52
|
40.85 Units on a scale
Standard Error 0.854
|
44.16 Units on a scale
Standard Error 1.040
|
41.32 Units on a scale
Standard Error 1.024
|
SECONDARY outcome
Timeframe: Baseline to Week 52 (patients with no moderate or severe exacerbations who completed the study were censored at the final visit date, which may have exceeded 52 weeks)Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
Time to first moderate or severe COPD exacerbation was calculated as the number of days from baseline to the day on which the patient experienced the first moderate or severe COPD exacerbation. A COPD exacerbation was considered to be moderate if treatment with systemic corticosteroids and/or antibiotic was required. A COPD exacerbation was considered to be severe if treatment for moderate severity and hospitalization was required.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=525 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=268 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=267 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)
|
363.0 Days
Interval 1.0 to 402.0
|
231.0 Days
Interval 1.0 to 380.0
|
364.0 Days
Interval 1.0 to 423.0
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
The number of puffs of rescue medication taken in the previous 12 hours was recorded in the Patient Diary in the morning and evening. The mean daily number of puffs of rescue medication taken was calculated by dividing the number of puffs of rescue medication per day over the 52 weeks of the study by the number of days with non-missing rescue medication data. Rescue medication data recorded during the 14 day run-in period was used to calculate the baseline. The analysis included the same covariates as the primary Outcome Measure. A positive change score indicates more puffs taken.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=523 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=263 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=263 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Taken During the Study (Baseline to Week 52)
|
-1.58 Puffs
Standard Error 0.151
|
-1.20 Puffs
Standard Error 0.184
|
-1.83 Puffs
Standard Error 0.183
|
SECONDARY outcome
Timeframe: Day 1, Week 26, and Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose. The analysis included the same covariates as the primary Outcome Measure.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=500 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=250 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=245 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52
Week 26 (n=451, 219, 233)
|
1.458 Liters
Standard Error 0.0161
|
1.324 Liters
Standard Error 0.0196
|
1.408 Liters
Standard Error 0.0191
|
|
Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52
Week 52 (n=416, 196, 210)
|
1.412 Liters
Standard Error 0.0157
|
1.303 Liters
Standard Error 0.0198
|
1.392 Liters
Standard Error 0.0191
|
|
Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52
Day 1
|
1.478 Liters
Standard Error 0.0088
|
1.388 Liters
Standard Error 0.0109
|
1.471 Liters
Standard Error 0.0109
|
SECONDARY outcome
Timeframe: Day 1, Week 12, Week 26, and Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
Trough FVC is defined as the average of the post-dose 23 h 15 min and the 23 h 45 min FVC values. Just prior to FVC measurement, patients performed normal tidal breathing. The patient was given a few breaths warning before being told "At the end of the next normal breath out, take a deep breath all the way in"; they were then verbally encouraged to make a maximal effort before relaxing. The analysis included the same covariates as the primary Outcome Measure.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=500 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=250 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=245 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52
Day 1
|
2.936 Liters
Standard Error 0.0165
|
2.757 Liters
Standard Error 0.0205
|
2.930 Liters
Standard Error 0.0206
|
|
Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52
Week 12 (n=442, 204, 217)
|
2.985 Liters
Standard Error 0.0265
|
2.802 Liters
Standard Error 0.0329
|
2.970 Liters
Standard Error 0.0323
|
|
Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52
Week 26 (n=418, 196, 208)
|
2.962 Liters
Standard Error 0.0299
|
2.758 Liters
Standard Error 0.0361
|
2.892 Liters
Standard Error 0.0355
|
|
Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52
Week 52 (n=395, 186, 201)
|
2.866 Liters
Standard Error 0.0335
|
2.687 Liters
Standard Error 0.0399
|
2.866 Liters
Standard Error 0.0383
|
SECONDARY outcome
Timeframe: 5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52Population: Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=144 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=79 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=76 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 4 (n=124, 64, 62)
|
1.577 Liters
Standard Error 0.0304
|
1.416 Liters
Standard Error 0.0384
|
1.519 Liters
Standard Error 0.0377
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 5 (n=125, 62, 63)
|
1.515 Liters
Standard Error 0.0293
|
1.359 Liters
Standard Error 0.0385
|
1.407 Liters
Standard Error 0.0372
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 15 (n=123, 62, 63)
|
1.529 Liters
Standard Error 0.0300
|
1.360 Liters
Standard Error 0.0394
|
1.425 Liters
Standard Error 0.0379
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, hour 1 (n=125, 62, 63)
|
1.557 Liters
Standard Error 0.0285
|
1.352 Liters
Standard Error 0.0376
|
1.472 Liters
Standard Error 0.0361
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 5 (n=119, 61, 58)
|
1.512 Liters
Standard Error 0.0305
|
1.394 Liters
Standard Error 0.0401
|
1.490 Liters
Standard Error 0.0394
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 15 (n=123, 61, 58)
|
1.520 Liters
Standard Error 0.0305
|
1.412 Liters
Standard Error 0.0403
|
1.491 Liters
Standard Error 0.0396
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 5 (n=135, 74, 74)
|
1.494 Liters
Standard Error 0.0135
|
1.416 Liters
Standard Error 0.0166
|
1.447 Liters
Standard Error 0.0164
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 1 (n=144, 76, 75)
|
1.583 Liters
Standard Error 0.0172
|
1.404 Liters
Standard Error 0.0213
|
1.514 Liters
Standard Error 0.0212
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 2 (n=144, 75, 75)
|
1.639 Liters
Standard Error 0.0202
|
1.445 Liters
Standard Error 0.0248
|
1.569 Liters
Standard Error 0.0247
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 3 (n=143, 74, 73)
|
1.629 Liters
Standard Error 0.0199
|
1.435 Liters
Standard Error 0.0249
|
1.587 Liters
Standard Error 0.0248
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 4 (n=144, 70, 74)
|
1.599 Liters
Standard Error 0.0221
|
1.415 Liters
Standard Error 0.0281
|
1.560 Liters
Standard Error 0.0275
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 6 (n=142, 71, 74)
|
1.578 Liters
Standard Error 0.0204
|
1.426 Liters
Standard Error 0.0255
|
1.575 Liters
Standard Error 0.0252
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, hour 1 (n=140, 68, 74)
|
1.575 Liters
Standard Error 0.0242
|
1.409 Liters
Standard Error 0.0305
|
1.540 Liters
Standard Error 0.0296
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 15 (n=130, 66, 71)
|
1.583 Liters
Standard Error 0.0267
|
1.441 Liters
Standard Error 0.0340
|
1.534 Liters
Standard Error 0.0326
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 30 (n=130, 67, 71)
|
1.603 Liters
Standard Error 0.0265
|
1.427 Liters
Standard Error 0.0335
|
1.549 Liters
Standard Error 0.0323
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 30 (n=123, 61, 58)
|
1.537 Liters
Standard Error 0.0332
|
1.391 Liters
Standard Error 0.0431
|
1.517 Liters
Standard Error 0.0424
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 22 (n=117, 60, 63)
|
1.420 Liters
Standard Error 0.0268
|
1.349 Liters
Standard Error 0.0350
|
1.371 Liters
Standard Error 0.0333
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 15 (n=126, 66, 67)
|
1.518 Liters
Standard Error 0.0269
|
1.456 Liters
Standard Error 0.0345
|
1.520 Liters
Standard Error 0.0335
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 45 (n=124, 65, 63)
|
1.513 Liters
Standard Error 0.0294
|
1.470 Liters
Standard Error 0.0377
|
1.488 Liters
Standard Error 0.0374
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 15 (n=124, 65, 65)
|
1.557 Liters
Standard Error 0.0309
|
1.422 Liters
Standard Error 0.0380
|
1.530 Liters
Standard Error 0.0377
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 30 (n=125, 65, 65)
|
1.570 Liters
Standard Error 0.0303
|
1.409 Liters
Standard Error 0.0370
|
1.535 Liters
Standard Error 0.0368
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 5 (n=125, 66, 63)
|
1.518 Liters
Standard Error 0.0281
|
1.393 Liters
Standard Error 0.0348
|
1.453 Liters
Standard Error 0.0351
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 30 (n=125, 65, 63)
|
1.576 Liters
Standard Error 0.0277
|
1.391 Liters
Standard Error 0.0349
|
1.502 Liters
Standard Error 0.0350
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 3 (n=124, 64, 64)
|
1.614 Liters
Standard Error 0.0303
|
1.442 Liters
Standard Error 0.0391
|
1.555 Liters
Standard Error 0.0380
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 5 (n=124, 60, 57)
|
1.456 Liters
Standard Error 0.0276
|
1.337 Liters
Standard Error 0.0368
|
1.377 Liters
Standard Error 0.0359
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 15 (n=122, 59, 58)
|
1.502 Liters
Standard Error 0.0282
|
1.380 Liters
Standard Error 0.0378
|
1.428 Liters
Standard Error 0.0364
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 16 (n=117, 53, 46)
|
1.377 Liters
Standard Error 0.0309
|
1.277 Liters
Standard Error 0.0422
|
1.329 Liters
Standard Error 0.0420
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 22 (n=118, 60, 52)
|
1.391 Liters
Standard Error 0.0302
|
1.314 Liters
Standard Error 0.0397
|
1.282 Liters
Standard Error 0.0396
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, 45 minutes (n=122, 61, 57)
|
1.434 Liters
Standard Error 0.0281
|
1.337 Liters
Standard Error 0.0372
|
1.359 Liters
Standard Error 0.0364
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 5 (n=128, 66, 70)
|
1.562 Liters
Standard Error 0.0268
|
1.417 Liters
Standard Error 0.0341
|
1.520 Liters
Standard Error 0.0326
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 15 (n=139, 75, 74)
|
1.548 Liters
Standard Error 0.0152
|
1.428 Liters
Standard Error 0.0185
|
1.485 Liters
Standard Error 0.0185
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 30 (n=143, 77, 74)
|
1.561 Liters
Standard Error 0.0180
|
1.409 Liters
Standard Error 0.0218
|
1.483 Liters
Standard Error 0.0219
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 8 (n=137, 70, 75)
|
1.544 Liters
Standard Error 0.0226
|
1.431 Liters
Standard Error 0.0284
|
1.545 Liters
Standard Error 0.0278
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day1, hour 10 (n=134, 72, 75)
|
1.546 Liters
Standard Error 0.0235
|
1.415 Liters
Standard Error 0.0290
|
1.537 Liters
Standard Error 0.0286
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 12 (n=130, 69, 70)
|
1.522 Liters
Standard Error 0.0254
|
1.369 Liters
Standard Error 0.0307
|
1.480 Liters
Standard Error 0.0306
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 15 (n=129, 71, 72)
|
1.471 Liters
Standard Error 0.0214
|
1.396 Liters
Standard Error 0.0259
|
1.481 Liters
Standard Error 0.0255
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 45 (n=128, 74, 75)
|
1.518 Liters
Standard Error 0.0210
|
1.446 Liters
Standard Error 0.0252
|
1.499 Liters
Standard Error 0.0249
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 5 (n=135, 65, 73)
|
1.494 Liters
Standard Error 0.0246
|
1.421 Liters
Standard Error 0.0315
|
1.490 Liters
Standard Error 0.0299
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 15 (n=133, 70, 72)
|
1.530 Liters
Standard Error 0.0246
|
1.411 Liters
Standard Error 0.0307
|
1.537 Liters
Standard Error 0.0303
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 30 (n= 139, 70, 74)
|
1.551 Liters
Standard Error 0.0236
|
1.417 Liters
Standard Error 0.0297
|
1.516 Liters
Standard Error 0.0289
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 5 (n=134, 66, 68)
|
1.550 Liters
Standard Error 0.0247
|
1.448 Liters
Standard Error 0.0319
|
1.525 Liters
Standard Error 0.0305
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 15 (n=136, 67, 70)
|
1.575 Liters
Standard Error 0.0239
|
1.452 Liters
Standard Error 0.0305
|
1.543 Liters
Standard Error 0.0295
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 30 (n=135, 67, 70)
|
1.630 Liters
Standard Error 0.0260
|
1.481 Liters
Standard Error 0.0327
|
1.584 Liters
Standard Error 0.0317
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 5 (n=130, 69, 70)
|
1.497 Liters
Standard Error 0.0254
|
1.385 Liters
Standard Error 0.0319
|
1.474 Liters
Standard Error 0.0315
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 15 (n=129, 67, 66)
|
1.523 Liters
Standard Error 0.0251
|
1.373 Liters
Standard Error 0.0317
|
1.481 Liters
Standard Error 0.0315
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 30 (n=133, 69, 67)
|
1.517 Liters
Standard Error 0.0275
|
1.362 Liters
Standard Error 0.0336
|
1.488 Liters
Standard Error 0.0335
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 1 (n=132, 67, 69)
|
1.557 Liters
Standard Error 0.0273
|
1.369 Liters
Standard Error 0.0341
|
1.519 Liters
Standard Error 0.0333
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 2 (n=129, 65, 68)
|
1.596 Liters
Standard Error 0.0290
|
1.434 Liters
Standard Error 0.0365
|
1.565 Liters
Standard Error 0.0353
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 3 (n=126, 64, 69)
|
1.600 Liters
Standard Error 0.0291
|
1.443 Liters
Standard Error 0.0375
|
1.566 Liters
Standard Error 0.0353
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 4 (n=124, 64, 68)
|
1.584 Liters
Standard Error 0.0319
|
1.442 Liters
Standard Error 0.0407
|
1.535 Liters
Standard Error 0.0383
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 6 (n=123, 63, 69)
|
1.558 Liters
Standard Error 0.0321
|
1.443 Liters
Standard Error 0.0407
|
1.520 Liters
Standard Error 0.0381
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 8 (n=121, 64, 69)
|
1.535 Liters
Standard Error 0.0310
|
1.408 Liters
Standard Error 0.0385
|
1.479 Liters
Standard Error 0.0374
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 10 (n=124, 61, 69)
|
1.541 Liters
Standard Error 0.0296
|
1.435 Liters
Standard Error 0.0392
|
1.532 Liters
Standard Error 0.0365
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 12 (n=122, 58, 68)
|
1.522 Liters
Standard Error 0.0313
|
1.422 Liters
Standard Error 0.0417
|
1.487 Liters
Standard Error 0.0382
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 16 (n=109, 56, 57)
|
1.431 Liters
Standard Error 0.0320
|
1.360 Liters
Standard Error 0.0425
|
1.378 Liters
Standard Error 0.0404
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 5 (n=123, 65, 64)
|
1.538 Liters
Standard Error 0.0296
|
1.430 Liters
Standard Error 0.0362
|
1.515 Liters
Standard Error 0.0359
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 15 (n=124, 65, 63)
|
1.535 Liters
Standard Error 0.0285
|
1.380 Liters
Standard Error 0.0354
|
1.479 Liters
Standard Error 0.0356
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 5 (n=123, 62, 64)
|
1.483 Liters
Standard Error 0.0278
|
1.361 Liters
Standard Error 0.0368
|
1.415 Liters
Standard Error 0.0352
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 15 (n=121, 61, 61)
|
1.521 Liters
Standard Error 0.0280
|
1.377 Liters
Standard Error 0.0373
|
1.464 Liters
Standard Error 0.0358
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 30 (n=125, 64, 64)
|
1.529 Liters
Standard Error 0.0285
|
1.353 Liters
Standard Error 0.0372
|
1.439 Liters
Standard Error 0.0359
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 1 (n=127, 64, 64)
|
1.546 Liters
Standard Error 0.0275
|
1.364 Liters
Standard Error 0.0359
|
1.462 Liters
Standard Error 0.0349
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 2 (n=124, 64, 63)
|
1.590 Liters
Standard Error 0.0317
|
1.422 Liters
Standard Error 0.0403
|
1.520 Liters
Standard Error 0.0395
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 15 (n=120, 55, 61)
|
1.477 Liters
Standard Error 0.0323
|
1.374 Liters
Standard Error 0.0422
|
1.416 Liters
Standard Error 0.0399
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 45 (n=117, 56, 61)
|
1.483 Liters
Standard Error 0.0296
|
1.401 Liters
Standard Error 0.0395
|
1.405 Liters
Standard Error 0.0376
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 30 (n=125, 62, 62)
|
1.567 Liters
Standard Error 0.0302
|
1.353 Liters
Standard Error 0.0398
|
1.452 Liters
Standard Error 0.0385
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 5 (n=120, 60, 57)
|
1.490 Liters
Standard Error 0.0269
|
1.357 Liters
Standard Error 0.0348
|
1.422 Liters
Standard Error 0.0341
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 15 (n=123, 60, 57)
|
1.529 Liters
Standard Error 0.0285
|
1.375 Liters
Standard Error 0.0369
|
1.452 Liters
Standard Error 0.0362
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 30 (n=123, 60, 58)
|
1.545 Liters
Standard Error 0.0287
|
1.368 Liters
Standard Error 0.0375
|
1.470 Liters
Standard Error 0.0366
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 30 (n=125, 62, 58)
|
1.483 Liters
Standard Error 0.0280
|
1.366 Liters
Standard Error 0.0370
|
1.407 Liters
Standard Error 0.0362
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 1 (n=125, 62, 57)
|
1.525 Liters
Standard Error 0.0271
|
1.356 Liters
Standard Error 0.0359
|
1.439 Liters
Standard Error 0.0352
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 2 (n=124, 61, 58)
|
1.554 Liters
Standard Error 0.0295
|
1.418 Liters
Standard Error 0.0393
|
1.479 Liters
Standard Error 0.0382
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 3 (n=123, 62, 56)
|
1.558 Liters
Standard Error 0.0263
|
1.384 Liters
Standard Error 0.0349
|
1.487 Liters
Standard Error 0.0345
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 4 (n=121, 60, 55)
|
1.535 Liters
Standard Error 0.0297
|
1.381 Liters
Standard Error 0.0395
|
1.468 Liters
Standard Error 0.0390
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 6 (n=118, 59, 54)
|
1.494 Liters
Standard Error 0.0294
|
1.370 Liters
Standard Error 0.0392
|
1.461 Liters
Standard Error 0.0388
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 8 (n=119, 59, 54)
|
1.473 Liters
Standard Error 0.0300
|
1.358 Liters
Standard Error 0.0398
|
1.418 Liters
Standard Error 0.0394
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 10 (n=119, 59, 55)
|
1.478 Liters
Standard Error 0.0304
|
1.349 Liters
Standard Error 0.0397
|
1.419 Liters
Standard Error 0.0391
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 12 (n=120, 58, 52)
|
1.451 Liters
Standard Error 0.0334
|
1.369 Liters
Standard Error 0.0446
|
1.347 Liters
Standard Error 0.0444
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, 15 minutes (n=121, 62, 57)
|
1.447 Liters
Standard Error 0.0287
|
1.362 Liters
Standard Error 0.0378
|
1.387 Liters
Standard Error 0.0371
|
SECONDARY outcome
Timeframe: 5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52Population: Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
Just prior to FVC measurement, patients performed normal tidal breathing. The patient was given a few breaths warning before being told "At the end of the next normal breath out, take a deep breath all the way in"; they were then verbally encouraged to make a maximal effort before relaxing. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=144 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=79 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=76 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 2 (n=144, 75, 75)
|
3.179 Liters
Standard Error 0.0373
|
2.802 Liters
Standard Error 0.0460
|
3.049 Liters
Standard Error 0.0461
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 3 (n=143, 74, 73)
|
3.190 Liters
Standard Error 0.0433
|
2.826 Liters
Standard Error 0.0526
|
3.119 Liters
Standard Error 0.0531
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 4 (n=144, 70, 74)
|
3.138 Liters
Standard Error 0.0414
|
2.783 Liters
Standard Error 0.0515
|
3.102 Liters
Standard Error 0.0512
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 6 (n=142, 71, 74)
|
3.173 Liters
Standard Error 0.0419
|
2.846 Liters
Standard Error 0.0514
|
3.148 Liters
Standard Error 0.0513
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day1, hour 10 (n=134, 72, 75)
|
3.134 Liters
Standard Error 0.0414
|
2.865 Liters
Standard Error 0.0514
|
3.119 Liters
Standard Error 0.0510
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 12 (n=130, 69, 70)
|
3.030 Liters
Standard Error 0.0444
|
2.709 Liters
Standard Error 0.0535
|
3.012 Liters
Standard Error 0.0537
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 15 (n=129, 71, 72)
|
2.991 Liters
Standard Error 0.0385
|
2.800 Liters
Standard Error 0.0478
|
2.988 Liters
Standard Error 0.0471
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 45 (n=128, 74, 75)
|
3.014 Liters
Standard Error 0.0364
|
2.817 Liters
Standard Error 0.0444
|
2.994 Liters
Standard Error 0.0442
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 5 (n=135, 65, 73)
|
3.051 Liters
Standard Error 0.0439
|
2.793 Liters
Standard Error 0.0553
|
3.014 Liters
Standard Error 0.0534
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 15 (n=133, 70, 72)
|
3.103 Liters
Standard Error 0.0443
|
2.790 Liters
Standard Error 0.0536
|
3.103 Liters
Standard Error 0.0536
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 30 (n= 139, 70, 74)
|
3.134 Liters
Standard Error 0.0420
|
2.825 Liters
Standard Error 0.0519
|
3.078 Liters
Standard Error 0.0513
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 5 (n=134, 66, 68)
|
3.139 Liters
Standard Error 0.0430
|
2.866 Liters
Standard Error 0.0551
|
3.071 Liters
Standard Error 0.0534
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 30 (n=135, 67, 70)
|
3.248 Liters
Standard Error 0.0540
|
2.884 Liters
Standard Error 0.0644
|
3.180 Liters
Standard Error 0.0636
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 30 (n=130, 67, 71)
|
3.231 Liters
Standard Error 0.0567
|
2.821 Liters
Standard Error 0.0675
|
3.149 Liters
Standard Error 0.0664
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 1 (n=132, 67, 69)
|
3.164 Liters
Standard Error 0.0543
|
2.737 Liters
Standard Error 0.0663
|
3.098 Liters
Standard Error 0.0655
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 3 (n=126, 64, 69)
|
3.240 Liters
Standard Error 0.0569
|
2.864 Liters
Standard Error 0.0713
|
3.146 Liters
Standard Error 0.0685
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 4 (n=124, 64, 68)
|
3.119 Liters
Standard Error 0.0576
|
2.745 Liters
Standard Error 0.0714
|
3.084 Liters
Standard Error 0.0686
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 8 (n=121, 64, 69)
|
3.083 Liters
Standard Error 0.0534
|
2.760 Liters
Standard Error 0.0657
|
3.011 Liters
Standard Error 0.0644
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 10 (n=124, 61, 69)
|
3.130 Liters
Standard Error 0.0581
|
2.860 Liters
Standard Error 0.0722
|
3.117 Liters
Standard Error 0.0692
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 12 (n=122, 58, 68)
|
3.072 Liters
Standard Error 0.0599
|
2.771 Liters
Standard Error 0.0770
|
3.020 Liters
Standard Error 0.0722
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 22 (n=117, 60, 63)
|
2.924 Liters
Standard Error 0.0517
|
2.673 Liters
Standard Error 0.0647
|
2.870 Liters
Standard Error 0.0629
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 15 (n=126, 66, 67)
|
3.091 Liters
Standard Error 0.0548
|
2.862 Liters
Standard Error 0.0676
|
3.110 Liters
Standard Error 0.0671
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 45 (n=124, 65, 63)
|
3.055 Liters
Standard Error 0.0507
|
2.826 Liters
Standard Error 0.0630
|
3.004 Liters
Standard Error 0.0638
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 5 (n=123, 65, 64)
|
3.156 Liters
Standard Error 0.0608
|
2.864 Liters
Standard Error 0.0719
|
3.104 Liters
Standard Error 0.0723
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 15 (n=124, 65, 65)
|
3.156 Liters
Standard Error 0.0576
|
2.801 Liters
Standard Error 0.0695
|
3.082 Liters
Standard Error 0.0699
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 30 (n=125, 65, 65)
|
3.198 Liters
Standard Error 0.0552
|
2.815 Liters
Standard Error 0.0676
|
3.112 Liters
Standard Error 0.0679
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 5 (n=125, 66, 63)
|
3.093 Liters
Standard Error 0.0526
|
2.781 Liters
Standard Error 0.0630
|
2.993 Liters
Standard Error 0.0643
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 15 (n=124, 65, 63)
|
3.112 Liters
Standard Error 0.0545
|
2.770 Liters
Standard Error 0.0655
|
3.029 Liters
Standard Error 0.0666
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 30 (n=125, 65, 63)
|
3.157 Liters
Standard Error 0.0559
|
2.778 Liters
Standard Error 0.0677
|
3.050 Liters
Standard Error 0.0688
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 15 (n=121, 61, 61)
|
3.041 Liters
Standard Error 0.0513
|
2.692 Liters
Standard Error 0.0652
|
2.976 Liters
Standard Error 0.0644
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 1 (n=127, 64, 64)
|
3.077 Liters
Standard Error 0.0520
|
2.678 Liters
Standard Error 0.0658
|
3.016 Liters
Standard Error 0.0651
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 15 (n=123, 62, 63)
|
3.016 Liters
Standard Error 0.0553
|
2.731 Liters
Standard Error 0.0691
|
2.898 Liters
Standard Error 0.0683
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 3 (n=123, 62, 56)
|
3.108 Liters
Standard Error 0.0648
|
2.716 Liters
Standard Error 0.0766
|
3.053 Liters
Standard Error 0.0779
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 4 (n=121, 60, 55)
|
3.021 Liters
Standard Error 0.0585
|
2.694 Liters
Standard Error 0.0724
|
2.978 Liters
Standard Error 0.0735
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 6 (n=118, 59, 54)
|
2.986 Liters
Standard Error 0.0614
|
2.690 Liters
Standard Error 0.0770
|
2.982 Liters
Standard Error 0.0781
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 8 (n=119, 59, 54)
|
2.961 Liters
Standard Error 0.0646
|
2.637 Liters
Standard Error 0.0793
|
2.942 Liters
Standard Error 0.0805
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 10 (n=119, 59, 55)
|
3.000 Liters
Standard Error 0.0701
|
2.687 Liters
Standard Error 0.0840
|
3.012 Liters
Standard Error 0.0844
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 12 (n=120, 58, 52)
|
2.881 Liters
Standard Error 0.0631
|
2.636 Liters
Standard Error 0.0831
|
2.849 Liters
Standard Error 0.0847
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 16 (n=117, 53, 46)
|
2.857 Liters
Standard Error 0.0694
|
2.542 Liters
Standard Error 0.0857
|
2.772 Liters
Standard Error 0.0873
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 22 (n=118, 60, 52)
|
2.812 Liters
Standard Error 0.0670
|
2.604 Liters
Standard Error 0.0810
|
2.716 Liters
Standard Error 0.0827
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, 15 minutes (n=121, 62, 57)
|
2.888 Liters
Standard Error 0.0595
|
2.678 Liters
Standard Error 0.0751
|
2.852 Liters
Standard Error 0.0755
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, 45 minutes (n=122, 61, 57)
|
2.855 Liters
Standard Error 0.0558
|
2.607 Liters
Standard Error 0.0700
|
2.797 Liters
Standard Error 0.0702
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 5 (n=123, 62, 64)
|
2.994 Liters
Standard Error 0.0528
|
2.700 Liters
Standard Error 0.0670
|
2.954 Liters
Standard Error 0.0658
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 30 (n=125, 64, 64)
|
3.054 Liters
Standard Error 0.0464
|
2.700 Liters
Standard Error 0.0597
|
2.994 Liters
Standard Error 0.0589
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 2 (n=124, 64, 63)
|
3.110 Liters
Standard Error 0.0516
|
2.771 Liters
Standard Error 0.0655
|
3.080 Liters
Standard Error 0.0650
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 3 (n=124, 64, 64)
|
3.210 Liters
Standard Error 0.0648
|
2.871 Liters
Standard Error 0.0765
|
3.176 Liters
Standard Error 0.0762
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 4 (n=124, 64, 62)
|
3.111 Liters
Standard Error 0.0551
|
2.791 Liters
Standard Error 0.0664
|
3.086 Liters
Standard Error 0.0664
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 15 (n=120, 55, 61)
|
3.056 Liters
Standard Error 0.0600
|
2.803 Liters
Standard Error 0.0749
|
2.932 Liters
Standard Error 0.0721
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 45 (n=117, 56, 61)
|
2.998 Liters
Standard Error 0.0512
|
2.752 Liters
Standard Error 0.0667
|
2.895 Liters
Standard Error 0.0646
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 5 (n=125, 62, 63)
|
3.023 Liters
Standard Error 0.0573
|
2.731 Liters
Standard Error 0.0715
|
2.881 Liters
Standard Error 0.0706
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 30 (n=125, 62, 62)
|
3.081 Liters
Standard Error 0.0555
|
2.687 Liters
Standard Error 0.0715
|
2.971 Liters
Standard Error 0.0708
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, hour 1 (n=125, 62, 63)
|
3.072 Liters
Standard Error 0.0564
|
2.703 Liters
Standard Error 0.0707
|
2.963 Liters
Standard Error 0.0699
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 5 (n=119, 61, 58)
|
3.033 Liters
Standard Error 0.0583
|
2.716 Liters
Standard Error 0.0744
|
3.069 Liters
Standard Error 0.0746
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 15 (n=123, 61, 58)
|
3.022 Liters
Standard Error 0.0539
|
2.695 Liters
Standard Error 0.0706
|
3.065 Liters
Standard Error 0.0699
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 30 (n=123, 61, 58)
|
3.057 Liters
Standard Error 0.0565
|
2.723 Liters
Standard Error 0.0734
|
3.098 Liters
Standard Error 0.0734
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 5 (n=120, 60, 57)
|
3.022 Liters
Standard Error 0.0596
|
2.731 Liters
Standard Error 0.0727
|
2.963 Liters
Standard Error 0.0726
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 15 (n=123, 60, 57)
|
3.042 Liters
Standard Error 0.0592
|
2.702 Liters
Standard Error 0.0726
|
2.937 Liters
Standard Error 0.0725
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 30 (n=123, 60, 58)
|
3.094 Liters
Standard Error 0.0613
|
2.731 Liters
Standard Error 0.0749
|
2.985 Liters
Standard Error 0.0747
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 5 (n=124, 60, 57)
|
2.940 Liters
Standard Error 0.0551
|
2.645 Liters
Standard Error 0.0701
|
2.860 Liters
Standard Error 0.0702
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 15 (n=122, 59, 58)
|
2.960 Liters
Standard Error 0.0518
|
2.640 Liters
Standard Error 0.0675
|
2.935 Liters
Standard Error 0.0666
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 30 (n=125, 62, 58)
|
2.939 Liters
Standard Error 0.0499
|
2.625 Liters
Standard Error 0.0650
|
2.929 Liters
Standard Error 0.0652
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 1 (n=125, 62, 57)
|
3.031 Liters
Standard Error 0.0564
|
2.617 Liters
Standard Error 0.0698
|
2.980 Liters
Standard Error 0.0704
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 2 (n=124, 61, 58)
|
3.062 Liters
Standard Error 0.0556
|
2.714 Liters
Standard Error 0.0689
|
3.021 Liters
Standard Error 0.0689
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 5 (n=135, 74, 74)
|
3.027 Liters
Standard Error 0.0304
|
2.826 Liters
Standard Error 0.0363
|
2.956 Liters
Standard Error 0.0363
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 15 (n=139, 75, 74)
|
3.050 Liters
Standard Error 0.0335
|
2.802 Liters
Standard Error 0.0403
|
2.991 Liters
Standard Error 0.0406
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 30 (n=143, 77, 74)
|
3.055 Liters
Standard Error 0.0343
|
2.752 Liters
Standard Error 0.0416
|
2.979 Liters
Standard Error 0.0422
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 1 (n=144, 76, 75)
|
3.148 Liters
Standard Error 0.0377
|
2.791 Liters
Standard Error 0.0460
|
3.041 Liters
Standard Error 0.0463
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 8 (n=137, 70, 75)
|
3.071 Liters
Standard Error 0.0404
|
2.804 Liters
Standard Error 0.0506
|
3.074 Liters
Standard Error 0.0498
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, hour 1 (n=140, 68, 74)
|
3.152 Liters
Standard Error 0.0434
|
2.770 Liters
Standard Error 0.0537
|
3.060 Liters
Standard Error 0.0528
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 15 (n=136, 67, 70)
|
3.165 Liters
Standard Error 0.0501
|
2.850 Liters
Standard Error 0.0611
|
3.092 Liters
Standard Error 0.0602
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 5 (n=128, 66, 70)
|
3.195 Liters
Standard Error 0.0543
|
2.826 Liters
Standard Error 0.0644
|
3.097 Liters
Standard Error 0.0632
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 15 (n=130, 66, 71)
|
3.167 Liters
Standard Error 0.0507
|
2.823 Liters
Standard Error 0.0615
|
3.101 Liters
Standard Error 0.0603
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 5 (n=130, 69, 70)
|
3.060 Liters
Standard Error 0.0492
|
2.728 Liters
Standard Error 0.0596
|
3.023 Liters
Standard Error 0.0596
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 15 (n=129, 67, 66)
|
3.081 Liters
Standard Error 0.0482
|
2.740 Liters
Standard Error 0.0588
|
3.018 Liters
Standard Error 0.0593
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 30 (n=133, 69, 67)
|
3.058 Liters
Standard Error 0.0479
|
2.696 Liters
Standard Error 0.0585
|
3.027 Liters
Standard Error 0.0591
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 2 (n=129, 65, 68)
|
3.190 Liters
Standard Error 0.0526
|
2.784 Liters
Standard Error 0.0664
|
3.155 Liters
Standard Error 0.0649
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 6 (n=123, 63, 69)
|
3.158 Liters
Standard Error 0.0594
|
2.852 Liters
Standard Error 0.0731
|
3.120 Liters
Standard Error 0.0700
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 16 (n=109, 56, 57)
|
2.933 Liters
Standard Error 0.0645
|
2.701 Liters
Standard Error 0.0800
|
2.880 Liters
Standard Error 0.0785
|
SECONDARY outcome
Timeframe: 5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=525 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=268 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=267 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 15 (n=502, 255, 254)
|
1.501 Liters
Standard Error 0.0074
|
1.359 Liters
Standard Error 0.0090
|
1.437 Liters
Standard Error 0.0090
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 30 (n=507, 252, 254)
|
1.524 Liters
Standard Error 0.0103
|
1.357 Liters
Standard Error 0.0126
|
1.468 Liters
Standard Error 0.0125
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 3 (n=510, 248, 252)
|
1.590 Liters
Standard Error 0.0088
|
1.389 Liters
Standard Error 0.0111
|
1.560 Liters
Standard Error 0.0109
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 4 (n=504, 239, 250)
|
1.590 Liters
Standard Error 0.0095
|
1.396 Liters
Standard Error 0.0121
|
1.549 Liters
Standard Error 0.0117
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 15 (n=481, 243, 239)
|
1.459 Liters
Standard Error 0.0093
|
1.364 Liters
Standard Error 0.0115
|
1.457 Liters
Standard Error 0.0115
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 45 (n=474, 239, 232)
|
1.482 Liters
Standard Error 0.0094
|
1.390 Liters
Standard Error 0.0117
|
1.473 Liters
Standard Error 0.0118
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 5 (n=498, 223, 243)
|
1.491 Liters
Standard Error 0.0123
|
1.368 Liters
Standard Error 0.0157
|
1.472 Liters
Standard Error 0.0151
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 15 (n=487, 229, 239)
|
1.527 Liters
Standard Error 0.0123
|
1.371 Liters
Standard Error 0.0154
|
1.514 Liters
Standard Error 0.0151
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 30 (n=503, 233, 242)
|
1.538 Liters
Standard Error 0.0122
|
1.368 Liters
Standard Error 0.0152
|
1.504 Liters
Standard Error 0.0150
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, hour 1 (n=501, 229, 240)
|
1.561 Liters
Standard Error 0.0121
|
1.379 Liters
Standard Error 0.0153
|
1.525 Liters
Standard Error 0.0150
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 5 (n=476, 221, 231)
|
1.509 Liters
Standard Error 0.0125
|
1.371 Liters
Standard Error 0.0161
|
1.488 Liters
Standard Error 0.0157
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 15 (n=479, 222, 234)
|
1.538 Liters
Standard Error 0.0126
|
1.389 Liters
Standard Error 0.0162
|
1.508 Liters
Standard Error 0.0157
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 30 (n=480, 223, 234)
|
1.564 Liters
Standard Error 0.0129
|
1.396 Liters
Standard Error 0.0165
|
1.525 Liters
Standard Error 0.0160
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 5 (n=454, 217, 227)
|
1.529 Liters
Standard Error 0.0126
|
1.366 Liters
Standard Error 0.0159
|
1.499 Liters
Standard Error 0.0157
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 15 (n=459, 220, 225)
|
1.550 Liters
Standard Error 0.0132
|
1.376 Liters
Standard Error 0.0164
|
1.515 Liters
Standard Error 0.0163
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 30 (n=460, 220, 226)
|
1.569 Liters
Standard Error 0.0125
|
1.378 Liters
Standard Error 0.0158
|
1.531 Liters
Standard Error 0.0157
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 5 (n=453, 212, 230)
|
1.502 Liters
Standard Error 0.0136
|
1.349 Liters
Standard Error 0.0173
|
1.477 Liters
Standard Error 0.0167
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 15 (n=448, 205, 222)
|
1.527 Liters
Standard Error 0.0131
|
1.352 Liters
Standard Error 0.0171
|
1.501 Liters
Standard Error 0.0166
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 3 (n=444, 204, 225)
|
1.592 Liters
Standard Error 0.0145
|
1.414 Liters
Standard Error 0.0186
|
1.561 Liters
Standard Error 0.0177
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 4 (n=437, 202, 224)
|
1.558 Liters
Standard Error 0.0152
|
1.416 Liters
Standard Error 0.0193
|
1.534 Liters
Standard Error 0.0183
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 15 (n=428, 209, 219)
|
1.530 Liters
Standard Error 0.0155
|
1.372 Liters
Standard Error 0.0189
|
1.491 Liters
Standard Error 0.0186
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 30 (n=433, 209, 220)
|
1.546 Liters
Standard Error 0.0160
|
1.372 Liters
Standard Error 0.0194
|
1.505 Liters
Standard Error 0.0190
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 1 (n=425, 206, 212)
|
1.541 Liters
Standard Error 0.0160
|
1.345 Liters
Standard Error 0.0193
|
1.487 Liters
Standard Error 0.0190
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 2 (n=420, 203, 208)
|
1.570 Liters
Standard Error 0.0176
|
1.388 Liters
Standard Error 0.0212
|
1.524 Liters
Standard Error 0.0210
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 3 (n=416, 204, 213)
|
1.570 Liters
Standard Error 0.0181
|
1.398 Liters
Standard Error 0.0216
|
1.526 Liters
Standard Error 0.0211
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 4 (n=416, 203, 208)
|
1.547 Liters
Standard Error 0.0175
|
1.384 Liters
Standard Error 0.0211
|
1.504 Liters
Standard Error 0.0208
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, hour 1 (n=412, 195, 215)
|
1.534 Liters
Standard Error 0.0171
|
1.331 Liters
Standard Error 0.0213
|
1.464 Liters
Standard Error 0.0205
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 5 (n=398, 189, 199)
|
1.489 Liters
Standard Error 0.0172
|
1.342 Liters
Standard Error 0.0218
|
1.459 Liters
Standard Error 0.0213
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 15 (n=405, 188, 201)
|
1.511 Liters
Standard Error 0.0171
|
1.344 Liters
Standard Error 0.0218
|
1.477 Liters
Standard Error 0.0211
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 30 (n=405, 189, 201)
|
1.518 Liters
Standard Error 0.0183
|
1.350 Liters
Standard Error 0.0229
|
1.496 Liters
Standard Error 0.0222
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 5 (n=386, 185, 199)
|
1.454 Liters
Standard Error 0.0155
|
1.336 Liters
Standard Error 0.0197
|
1.429 Liters
Standard Error 0.0190
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 15 (n=391, 187, 203)
|
1.496 Liters
Standard Error 0.0156
|
1.341 Liters
Standard Error 0.0199
|
1.462 Liters
Standard Error 0.0192
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 30 (n=392, 186, 204)
|
1.504 Liters
Standard Error 0.0166
|
1.341 Liters
Standard Error 0.0210
|
1.475 Liters
Standard Error 0.0200
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 5 (n=401, 188, 197)
|
1.436 Liters
Standard Error 0.0155
|
1.305 Liters
Standard Error 0.0200
|
1.419 Liters
Standard Error 0.0195
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 15 (n=394, 183, 200)
|
1.471 Liters
Standard Error 0.0159
|
1.323 Liters
Standard Error 0.0208
|
1.451 Liters
Standard Error 0.0198
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 30 (n=402, 189, 202)
|
1.471 Liters
Standard Error 0.0164
|
1.319 Liters
Standard Error 0.0209
|
1.451 Liters
Standard Error 0.0202
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 1 (n=404, 190, 201)
|
1.499 Liters
Standard Error 0.0161
|
1.325 Liters
Standard Error 0.0205
|
1.482 Liters
Standard Error 0.0198
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 2 (n=402, 186, 202)
|
1.526 Liters
Standard Error 0.0177
|
1.363 Liters
Standard Error 0.0224
|
1.511 Liters
Standard Error 0.0214
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, minute 15 (n=388, 183, 198)
|
1.419 Liters
Standard Error 0.0169
|
1.303 Liters
Standard Error 0.0215
|
1.397 Liters
Standard Error 0.0205
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 30 (n=455, 212, 226)
|
1.522 Liters
Standard Error 0.0139
|
1.352 Liters
Standard Error 0.0176
|
1.491 Liters
Standard Error 0.0170
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 1 (n=455, 210, 227)
|
1.556 Liters
Standard Error 0.0139
|
1.364 Liters
Standard Error 0.0178
|
1.528 Liters
Standard Error 0.0171
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 2 (n=446, 207, 225)
|
1.595 Liters
Standard Error 0.0145
|
1.423 Liters
Standard Error 0.0185
|
1.558 Liters
Standard Error 0.0178
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 15 (n=430, 200, 214)
|
1.481 Liters
Standard Error 0.0143
|
1.381 Liters
Standard Error 0.0183
|
1.457 Liters
Standard Error 0.0177
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 5 (n=495, 255, 253)
|
1.443 Liters
Standard Error 0.0067
|
1.357 Liters
Standard Error 0.0081
|
1.402 Liters
Standard Error 0.0081
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 1 (n=511, 256, 254)
|
1.552 Liters
Standard Error 0.0082
|
1.353 Liters
Standard Error 0.0101
|
1.484 Liters
Standard Error 0.0101
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 2 (n=513, 253, 252)
|
1.612 Liters
Standard Error 0.0090
|
1.397 Liters
Standard Error 0.0113
|
1.549 Liters
Standard Error 0.0112
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 45 (n=426, 195, 205)
|
1.493 Liters
Standard Error 0.0149
|
1.413 Liters
Standard Error 0.0190
|
1.472 Liters
Standard Error 0.0187
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 5 (n=429, 207, 218)
|
1.514 Liters
Standard Error 0.0151
|
1.373 Liters
Standard Error 0.0185
|
1.487 Liters
Standard Error 0.0181
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 5 (n=430, 206, 218)
|
1.495 Liters
Standard Error 0.0159
|
1.351 Liters
Standard Error 0.0198
|
1.464 Liters
Standard Error 0.0192
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 15 (n=430, 207, 220)
|
1.525 Liters
Standard Error 0.0164
|
1.362 Liters
Standard Error 0.0203
|
1.495 Liters
Standard Error 0.0196
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 30 (n=431, 207, 221)
|
1.544 Liters
Standard Error 0.0164
|
1.362 Liters
Standard Error 0.0203
|
1.498 Liters
Standard Error 0.0195
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 5 (421, 202, 213)
|
1.479 Liters
Standard Error 0.0153
|
1.339 Liters
Standard Error 0.0189
|
1.429 Liters
Standard Error 0.0185
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 15 (n=414, 200, 207)
|
1.504 Liters
Standard Error 0.0155
|
1.340 Liters
Standard Error 0.0193
|
1.458 Liters
Standard Error 0.0191
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 30 (n=424, 206, 213)
|
1.513 Liters
Standard Error 0.0161
|
1.341 Liters
Standard Error 0.0196
|
1.451 Liters
Standard Error 0.0193
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 15 (n=405, 187, 202)
|
1.464 Liters
Standard Error 0.0175
|
1.326 Liters
Standard Error 0.0217
|
1.415 Liters
Standard Error 0.0212
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 45 (n=401, 185, 198)
|
1.474 Liters
Standard Error 0.0175
|
1.354 Liters
Standard Error 0.0218
|
1.426 Liters
Standard Error 0.0215
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 5 (n=408, 194, 212)
|
1.481 Liters
Standard Error 0.0167
|
1.338 Liters
Standard Error 0.0210
|
1.422 Liters
Standard Error 0.0202
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 15 (n=407, 191, 214)
|
1.508 Liters
Standard Error 0.0172
|
1.333 Liters
Standard Error 0.0215
|
1.443 Liters
Standard Error 0.0206
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 30 (n=410, 196, 215)
|
1.518 Liters
Standard Error 0.0172
|
1.331 Liters
Standard Error 0.0214
|
1.444 Liters
Standard Error 0.0206
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 3 (n=400, 186, 199)
|
1.525 Liters
Standard Error 0.0171
|
1.344 Liters
Standard Error 0.0215
|
1.509 Liters
Standard Error 0.0207
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 4 (n=397, 184, 199)
|
1.504 Liters
Standard Error 0.0176
|
1.346 Liters
Standard Error 0.0222
|
1.501 Liters
Standard Error 0.0213
|
|
Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, minute 45 (n=395, 185, 199)
|
1.424 Liters
Standard Error 0.0165
|
1.320 Liters
Standard Error 0.0210
|
1.411 Liters
Standard Error 0.0201
|
SECONDARY outcome
Timeframe: 5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
Just prior to FVC measurement, patients performed normal tidal breathing. The patient was given a few breaths warning before being told "At the end of the next normal breath out, take a deep breath all the way in"; they were then verbally encouraged to make a maximal effort before relaxing. The analysis included the same covariates as the primary Outcome Measure. Data was not collected at all time points for all Days and Weeks.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=525 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=268 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=267 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 15 (n=502, 255, 254)
|
2.982 Liters
Standard Error 0.0164
|
2.719 Liters
Standard Error 0.0199
|
2.903 Liters
Standard Error 0.0198
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 30 (n=507, 252, 254)
|
3.004 Liters
Standard Error 0.0177
|
2.692 Liters
Standard Error 0.0219
|
2.937 Liters
Standard Error 0.0217
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 1 (n=511, 256, 254)
|
3.074 Liters
Standard Error 0.0173
|
2.732 Liters
Standard Error 0.0214
|
2.975 Liters
Standard Error 0.0213
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 2 (n=513, 253, 252)
|
3.119 Liters
Standard Error 0.0182
|
2.762 Liters
Standard Error 0.0227
|
3.033 Liters
Standard Error 0.0226
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 3 (n=510, 248, 252)
|
3.129 Liters
Standard Error 0.0193
|
2.811 Liters
Standard Error 0.0243
|
3.073 Liters
Standard Error 0.0239
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 4 (n=504, 239, 250)
|
3.076 Liters
Standard Error 0.0192
|
2.767 Liters
Standard Error 0.0244
|
3.031 Liters
Standard Error 0.0237
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 45 (n=474, 239, 232)
|
2.930 Liters
Standard Error 0.0178
|
2.749 Liters
Standard Error 0.0221
|
2.923 Liters
Standard Error 0.0224
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 5 (n=498, 223, 243)
|
2.984 Liters
Standard Error 0.0222
|
2.760 Liters
Standard Error 0.0282
|
2.980 Liters
Standard Error 0.0272
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 15 (n=487, 229, 239)
|
3.016 Liters
Standard Error 0.0220
|
2.748 Liters
Standard Error 0.0274
|
3.030 Liters
Standard Error 0.0270
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, minute 30 (n=503, 233, 242)
|
3.028 Liters
Standard Error 0.0212
|
2.756 Liters
Standard Error 0.0269
|
3.018 Liters
Standard Error 0.0265
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 15, hour 1 (n=501, 229, 240)
|
3.068 Liters
Standard Error 0.0213
|
2.757 Liters
Standard Error 0.0271
|
3.023 Liters
Standard Error 0.0267
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 5 (n=476, 221, 231)
|
3.004 Liters
Standard Error 0.0215
|
2.768 Liters
Standard Error 0.0277
|
3.011 Liters
Standard Error 0.0270
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 15 (n=479, 222, 234)
|
3.024 Liters
Standard Error 0.0234
|
2.771 Liters
Standard Error 0.0294
|
3.024 Liters
Standard Error 0.0286
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 5, minute 30 (n=480, 223, 234)
|
3.085 Liters
Standard Error 0.0243
|
2.804 Liters
Standard Error 0.0305
|
3.063 Liters
Standard Error 0.0297
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 15 (n=459, 220, 225)
|
3.050 Liters
Standard Error 0.0257
|
2.764 Liters
Standard Error 0.0312
|
3.046 Liters
Standard Error 0.0311
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 30 (n=460, 220, 226)
|
3.079 Liters
Standard Error 0.0265
|
2.768 Liters
Standard Error 0.0322
|
3.079 Liters
Standard Error 0.0319
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 15 (n=448, 205, 222)
|
3.003 Liters
Standard Error 0.0252
|
2.735 Liters
Standard Error 0.0316
|
3.004 Liters
Standard Error 0.0307
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 30 (n=455, 212, 226)
|
2.985 Liters
Standard Error 0.0251
|
2.707 Liters
Standard Error 0.0314
|
2.987 Liters
Standard Error 0.0306
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 1 (n=455, 210, 227)
|
3.062 Liters
Standard Error 0.0267
|
2.741 Liters
Standard Error 0.0333
|
3.048 Liters
Standard Error 0.0322
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 2 (n=446, 207, 225)
|
3.093 Liters
Standard Error 0.0266
|
2.801 Liters
Standard Error 0.0335
|
3.065 Liters
Standard Error 0.0324
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 3 (n=444, 204, 225)
|
3.129 Liters
Standard Error 0.0275
|
2.839 Liters
Standard Error 0.0346
|
3.096 Liters
Standard Error 0.0332
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 4 (n=437, 202, 224)
|
3.050 Liters
Standard Error 0.0278
|
2.793 Liters
Standard Error 0.0349
|
3.054 Liters
Standard Error 0.0333
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 15 (n=430, 200, 214)
|
2.991 Liters
Standard Error 0.0282
|
2.799 Liters
Standard Error 0.0349
|
2.985 Liters
Standard Error 0.0341
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, hour 23, minute 45 (n=426, 195, 205)
|
2.977 Liters
Standard Error 0.0268
|
2.799 Liters
Standard Error 0.0336
|
2.946 Liters
Standard Error 0.0332
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 5 (n=429, 207, 218)
|
3.016 Liters
Standard Error 0.0301
|
2.753 Liters
Standard Error 0.0362
|
3.009 Liters
Standard Error 0.0355
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 15 (n=428, 209, 219)
|
3.029 Liters
Standard Error 0.0293
|
2.737 Liters
Standard Error 0.0353
|
3.002 Liters
Standard Error 0.0348
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 16, minute 30 (n=433, 209, 220)
|
3.063 Liters
Standard Error 0.0298
|
2.747 Liters
Standard Error 0.0359
|
3.036 Liters
Standard Error 0.0353
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 5 (n=430, 206, 218)
|
2.985 Liters
Standard Error 0.0286
|
2.744 Liters
Standard Error 0.0349
|
2.966 Liters
Standard Error 0.0338
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 15 (n=430, 207, 220)
|
3.020 Liters
Standard Error 0.0293
|
2.749 Liters
Standard Error 0.0356
|
2.994 Liters
Standard Error 0.0345
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 20, minute 30 (n=431, 207, 221)
|
3.058 Liters
Standard Error 0.0309
|
2.774 Liters
Standard Error 0.0374
|
3.028 Liters
Standard Error 0.0362
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 5 (421, 202, 213)
|
2.956 Liters
Standard Error 0.0289
|
2.733 Liters
Standard Error 0.0352
|
2.945 Liters
Standard Error 0.0345
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 15 (n=414, 200, 207)
|
2.980 Liters
Standard Error 0.0298
|
2.713 Liters
Standard Error 0.0363
|
2.959 Liters
Standard Error 0.0360
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, minute 30 (n=424, 206, 213)
|
2.983 Liters
Standard Error 0.0282
|
2.715 Liters
Standard Error 0.0342
|
2.949 Liters
Standard Error 0.0337
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 1 (n=425, 206, 212)
|
3.034 Liters
Standard Error 0.0293
|
2.721 Liters
Standard Error 0.0352
|
2.997 Liters
Standard Error 0.0346
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 2 (n=420, 203, 208)
|
3.049 Liters
Standard Error 0.0308
|
2.777 Liters
Standard Error 0.0370
|
3.036 Liters
Standard Error 0.0366
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 4 (n=416, 203, 208)
|
3.022 Liters
Standard Error 0.0312
|
2.776 Liters
Standard Error 0.0369
|
3.021 Liters
Standard Error 0.0364
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 15 (n=405, 187, 202)
|
2.971 Liters
Standard Error 0.0321
|
2.758 Liters
Standard Error 0.0387
|
2.901 Liters
Standard Error 0.0379
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 5 (n=408, 194, 212)
|
2.967 Liters
Standard Error 0.0321
|
2.713 Liters
Standard Error 0.0387
|
2.919 Liters
Standard Error 0.0374
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 15 (n=407, 191, 214)
|
2.983 Liters
Standard Error 0.0327
|
2.718 Liters
Standard Error 0.0392
|
2.948 Liters
Standard Error 0.0376
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, hour 1 (n=412, 195, 215)
|
3.014 Liters
Standard Error 0.0336
|
2.711 Liters
Standard Error 0.0400
|
2.959 Liters
Standard Error 0.0385
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 5 (n=398, 189, 199)
|
2.982 Liters
Standard Error 0.0344
|
2.727 Liters
Standard Error 0.0415
|
2.983 Liters
Standard Error 0.0406
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 15 (n=405, 188, 201)
|
3.001 Liters
Standard Error 0.0336
|
2.713 Liters
Standard Error 0.0410
|
3.001 Liters
Standard Error 0.0398
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 42, minute 30 (n=405, 189, 201)
|
3.016 Liters
Standard Error 0.0345
|
2.734 Liters
Standard Error 0.0419
|
3.021 Liters
Standard Error 0.0408
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 5 (n=386, 185, 199)
|
2.925 Liters
Standard Error 0.0328
|
2.729 Liters
Standard Error 0.0393
|
2.942 Liters
Standard Error 0.0381
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 30 (n=402, 189, 202)
|
2.923 Liters
Standard Error 0.0325
|
2.666 Liters
Standard Error 0.0391
|
2.962 Liters
Standard Error 0.0378
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 1 (n=404, 190, 201)
|
2.992 Liters
Standard Error 0.0339
|
2.696 Liters
Standard Error 0.0405
|
3.011 Liters
Standard Error 0.0393
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 2 (n=402, 186, 202)
|
2.997 Liters
Standard Error 0.0354
|
2.727 Liters
Standard Error 0.0421
|
3.005 Liters
Standard Error 0.0405
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 3 (n=400, 186, 199)
|
3.029 Liters
Standard Error 0.0359
|
2.742 Liters
Standard Error 0.0427
|
3.020 Liters
Standard Error 0.0413
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 4 (n=397, 184, 199)
|
2.984 Liters
Standard Error 0.0359
|
2.725 Liters
Standard Error 0.0425
|
2.991 Liters
Standard Error 0.0410
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, minute 45 (n=395, 185, 199)
|
2.869 Liters
Standard Error 0.0342
|
2.694 Liters
Standard Error 0.0406
|
2.868 Liters
Standard Error 0.0390
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 5 (n=401, 188, 197)
|
2.899 Liters
Standard Error 0.0309
|
2.673 Liters
Standard Error 0.0377
|
2.916 Liters
Standard Error 0.0367
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 3 (n=416, 204, 213)
|
3.097 Liters
Standard Error 0.0331
|
2.831 Liters
Standard Error 0.0389
|
3.065 Liters
Standard Error 0.0381
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 26, hour 23, minute 45 (n=401, 185, 198)
|
2.952 Liters
Standard Error 0.0305
|
2.759 Liters
Standard Error 0.0373
|
2.883 Liters
Standard Error 0.0368
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 34, minute 30 (n=410, 196, 215)
|
3.002 Liters
Standard Error 0.0333
|
2.690 Liters
Standard Error 0.0400
|
2.947 Liters
Standard Error 0.0386
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 15 (n=391, 187, 203)
|
2.971 Liters
Standard Error 0.0330
|
2.729 Liters
Standard Error 0.0398
|
2.962 Liters
Standard Error 0.0384
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 50, minute 30 (n=392, 186, 204)
|
2.999 Liters
Standard Error 0.0342
|
2.731 Liters
Standard Error 0.0409
|
2.998 Liters
Standard Error 0.0394
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, minute 15 (n=394, 183, 200)
|
2.942 Liters
Standard Error 0.0314
|
2.701 Liters
Standard Error 0.0389
|
2.969 Liters
Standard Error 0.0371
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 52, hour 23, minute 15 (n=388, 183, 198)
|
2.866 Liters
Standard Error 0.0349
|
2.675 Liters
Standard Error 0.0419
|
2.865 Liters
Standard Error 0.0402
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, minute 5 (n=495, 255, 253)
|
2.915 Liters
Standard Error 0.0145
|
2.731 Liters
Standard Error 0.0174
|
2.856 Liters
Standard Error 0.0174
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Day 1, hour 23, minute 15 (n=481, 243, 239)
|
2.926 Liters
Standard Error 0.0178
|
2.745 Liters
Standard Error 0.0220
|
2.923 Liters
Standard Error 0.0220
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 9, minute 5 (n=454, 217, 227)
|
3.047 Liters
Standard Error 0.0262
|
2.767 Liters
Standard Error 0.0313
|
3.029 Liters
Standard Error 0.0309
|
|
Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
Week 12, minute 5 (n=453, 212, 230)
|
2.991 Liters
Standard Error 0.0253
|
2.726 Liters
Standard Error 0.0313
|
2.978 Liters
Standard Error 0.0304
|
SECONDARY outcome
Timeframe: From 5 minutes to 4 hours post-dose at Day 1 and Weeks 12, 26, and 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 3, and 4 hours post-dose. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included the same covariates as the primary Outcome Measure.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=519 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=266 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=264 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at Day 1 and Weeks 12, 26, and 52
Day 1
|
1.570 Liters
Standard Error 0.0075
|
1.373 Liters
Standard Error 0.0092
|
1.514 Liters
Standard Error 0.0092
|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at Day 1 and Weeks 12, 26, and 52
Week 12 (n=460, 214, 232)
|
1.560 Liters
Standard Error 0.0134
|
1.384 Liters
Standard Error 0.0170
|
1.531 Liters
Standard Error 0.0164
|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at Day 1 and Weeks 12, 26, and 52
Week 26 (n=430, 206, 216)
|
1.546 Liters
Standard Error 0.0160
|
1.369 Liters
Standard Error 0.0194
|
1.495 Liters
Standard Error 0.0190
|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at Day 1 and Weeks 12, 26, and 52
Week 52 (n=405, 192, 203)
|
1.502 Liters
Standard Error 0.0162
|
1.336 Liters
Standard Error 0.0203
|
1.487 Liters
Standard Error 0.0196
|
SECONDARY outcome
Timeframe: From 5 minutes to 12 hours post-dose at Day 1 and Weeks 12 and 52Population: Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 3, 4, 6, 8 10, and 12 hours post-dose. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included the same covariates as the primary Outcome Measure.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=144 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=77 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=76 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose at Day 1 and Weeks 12 and 52
Week 52 (n=125, 62, 58)
|
1.492 Liters
Standard Error 0.0265
|
1.364 Liters
Standard Error 0.0352
|
1.424 Liters
Standard Error 0.0344
|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose at Day 1 and Weeks 12 and 52
Day 1
|
1.566 Liters
Standard Error 0.0168
|
1.407 Liters
Standard Error 0.0207
|
1.534 Liters
Standard Error 0.0206
|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose at Day 1 and Weeks 12 and 52
Week 12 (n=133, 69, 70)
|
1.539 Liters
Standard Error 0.0261
|
1.398 Liters
Standard Error 0.0324
|
1.505 Liters
Standard Error 0.0320
|
SECONDARY outcome
Timeframe: From 5 minutes to 23 hours 45 minutes post-dose at Weeks 12 and 52Population: Full Analysis Set (FAS), serial spirometry subgroup: A subgroup of approximately one third of all randomized patients who received at least 1 dose of study medication.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included the same covariates as the primary Outcome Measure.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=133 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=69 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=70 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes and From 12 Hours to 23 Hours 45 Minutes Post-dose at Weeks 12 and 52
Week 12
|
1.486 Liters
Standard Error 0.0236
|
1.380 Liters
Standard Error 0.0298
|
1.459 Liters
Standard Error 0.0294
|
|
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes and From 12 Hours to 23 Hours 45 Minutes Post-dose at Weeks 12 and 52
Week 52 (n=125, 62, 58)
|
1.445 Liters
Standard Error 0.0261
|
1.339 Liters
Standard Error 0.0346
|
1.379 Liters
Standard Error 0.0338
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
The number of moderate or severe exacerbations of COPD per year during the study was calculated by dividing the total number of exacerbations during the study by the total number of years of treatment. A COPD exacerbation was considered to be moderate if treatment with systemic corticosteroids and/or antibiotic was required. A COPD exacerbation was considered to be severe if treatment for moderate severity and hospitalization was required.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=525 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=268 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=267 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) Per Year During the Study (Baseline to Week 52)
|
0.54 Exacerbations per treatment year
Interval 0.496 to 0.869
|
0.80 Exacerbations per treatment year
Interval 0.586 to 1.105
|
0.62 Exacerbations per treatment year
Interval 0.614 to 1.085
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
A COPD exacerbation was considered to be moderate if treatment with systemic corticosteroids and/or antibiotic was required. A COPD exacerbation was considered to be severe if treatment for moderate severity and hospitalization was required.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=524 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=266 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=266 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Percentage of Patients Who Experienced a Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)
|
32.8 Percentage of participants
|
40.2 Percentage of participants
|
30.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
A night with "no nighttime awakenings" was defined as any night where the patient did not wake up due to 1 or more of 6 symptoms (respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and breathlessness). Symptoms occurring during the previous 12 hours were recorded each morning and evening by the patient in an electronic diary. The percentage of nights with 'no nighttime awakenings' was calculated as the total number of nights with "no nighttime awakenings" over the 52 week treatment period divided by the total number of nights where diary recordings were made.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=523 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=263 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=262 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Percentage of Nights With "no Nighttime Awakenings" During the Study (Baseline to Week 52)
|
57.36 Percentage of nights
Standard Error 1.842
|
52.15 Percentage of nights
Standard Error 2.239
|
55.47 Percentage of nights
Standard Error 2.230
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
A day with "no daytime symptoms" was defined as any day where the patient recorded no cough, no wheeze, no production of sputum, no feeling of breathlessness (other than when running), and no puffs of rescue medication during the previous 12 hours in evening entry in the electronic patient diary. The percentage of days with "no daytime symptoms" was calculated as the total number of days with "no daytime symptoms" over the 52 week treatment period divided by the total number of days where diary recordings were made.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=522 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=263 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=263 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Percentage of Days With "no Daytime Symptoms" During the Study (Baseline to Week 52)
|
6.54 Percentage of days
Standard Error 1.208
|
3.81 Percentage of days
Standard Error 1.431
|
7.14 Percentage of days
Standard Error 1.424
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
A "day able to perform usual daily activities" was defined as any day where the patient recorded in their electronic diary in the evening that they were not prevented from performing their usual daily activities due to respiratory symptoms during the previous 12 hours. The percentage of "days able to perform usual daily activities" was calculated as the total number of "days able to perform usual daily activities" over the 52 week treatment period divided by the total number of days where diary recordings were made.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=522 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=263 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=263 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Percentage of "Days Able to Perform Usual Daily Activities" During the Study (Baseline to Week 52)
|
38.02 Percentage of days
Standard Error 1.883
|
36.18 Percentage of days
Standard Error 2.270
|
38.09 Percentage of days
Standard Error 2.259
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study medication.
The daily total symptom score was defined as the sum of the morning and evening patient self-reported diary assessments of 6 symptoms (respiratory symptoms/impact on daily activities, cough, wheeze, amount of sputum, color of sputum, and breathlessness). Means for baseline (14 day maximum run-in period) and the 52 week treatment period were calculated. Mean scores ranged from 0-18, with a higher score indicating worse symptoms. A negative change score indicated improvement.
Outcome measures
| Measure |
Glycopyrronium Bromide 50 μg
n=523 Participants
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=263 Participants
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=263 Participants
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Change From Baseline in the Mean Daily Total Symptom Score During the Study (Baseline to Week 52)
|
-1.85 Units on a scale
Standard Error 0.125
|
-1.42 Units on a scale
Standard Error 0.149
|
-1.87 Units on a scale
Standard Error 0.149
|
Adverse Events
Glycopyrronium Bromide 50 μg
Serious events: 65 serious events
Other events: 305 other events
Deaths: 0 deaths
Placebo to Glycopyrronium Bromide
Serious events: 43 serious events
Other events: 164 other events
Deaths: 0 deaths
Tiotropium 18 μg
Serious events: 40 serious events
Other events: 156 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Glycopyrronium Bromide 50 μg
n=525 participants at risk
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=268 participants at risk
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=267 participants at risk
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Cardiac disorders
Acute coronary syndrome
|
0.38%
2/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Cardiac disorders
Angina pectoris
|
0.19%
1/525
|
1.1%
3/268
|
0.00%
0/267
|
|
Cardiac disorders
Atrial fibrillation
|
0.76%
4/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Cardiac disorders
Atrial flutter
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Cardiac disorders
Bradycardia
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Cardiac disorders
Cardiac failure
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Cardiac disorders
Cardiovascular insufficiency
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Cardiac disorders
Congestive cardiomyopathy
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Cardiac disorders
Right ventricular failure
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Cardiac disorders
Tachyarrhythmia
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/525
|
0.75%
2/268
|
0.00%
0/267
|
|
Eye disorders
Retinal detachment
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Abdominal mass
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Abdominal pain
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Colitis
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/525
|
0.00%
0/268
|
0.75%
2/267
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Rectal ulcer haemorrhage
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Subileus
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
General disorders
Asthenia
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
General disorders
Impaired healing
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
General disorders
Influenza like illness
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
General disorders
Non-cardiac chest pain
|
0.19%
1/525
|
0.00%
0/268
|
1.1%
3/267
|
|
General disorders
Pyrexia
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
General disorders
Ulcer haemorrhage
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.38%
2/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Infections and infestations
Bronchitis
|
0.57%
3/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Infections and infestations
Cellulitis
|
0.19%
1/525
|
0.37%
1/268
|
0.37%
1/267
|
|
Infections and infestations
Clostridial infection
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Infections and infestations
Diverticulitis
|
0.38%
2/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Infections and infestations
Gastroenteritis
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Infections and infestations
Herpes zoster
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/525
|
0.37%
1/268
|
0.75%
2/267
|
|
Infections and infestations
Lower respiratory tract infection
|
0.38%
2/525
|
0.37%
1/268
|
0.37%
1/267
|
|
Infections and infestations
Pneumococcal sepsis
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Infections and infestations
Pneumonia
|
1.3%
7/525
|
2.6%
7/268
|
1.5%
4/267
|
|
Infections and infestations
Pneumonia bacterial
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Infections and infestations
Pseudomonas infection
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Infections and infestations
Pyothorax
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Infections and infestations
Sepsis
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Infections and infestations
Sinusitis
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Infections and infestations
Upper respiratory tract infection
|
0.19%
1/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Infections and infestations
Upper respiratory tract infection bacterial
|
0.38%
2/525
|
1.1%
3/268
|
0.75%
2/267
|
|
Infections and infestations
Viral infection
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/525
|
0.00%
0/268
|
0.75%
2/267
|
|
Injury, poisoning and procedural complications
Burns third degree
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Collapse of lung
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Heat exhaustion
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.38%
2/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Incisional hernia, obstructive
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Injury
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Limb crushing injury
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Spinal column injury
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/525
|
0.37%
1/268
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Splenic injury
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Stab wound
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Metabolism and nutrition disorders
Dehydration
|
0.76%
4/525
|
0.75%
2/268
|
0.00%
0/267
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.19%
1/525
|
0.37%
1/268
|
0.37%
1/267
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Biliary neoplasm
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lentigo maligna stage unspecified
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung squamous cell carcinoma stage unspecified
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Polycythaemia vera
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Nervous system disorders
Carotid artery stenosis
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Nervous system disorders
Convulsion
|
0.00%
0/525
|
0.37%
1/268
|
0.37%
1/267
|
|
Nervous system disorders
Dizziness
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Nervous system disorders
Syncope
|
0.57%
3/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Nervous system disorders
Transient ischaemic attack
|
0.57%
3/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Nervous system disorders
Vertebrobasilar insufficiency
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Psychiatric disorders
Anxiety disorder
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Psychiatric disorders
Depression
|
0.00%
0/525
|
0.37%
1/268
|
0.37%
1/267
|
|
Psychiatric disorders
Mental disorder
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Renal and urinary disorders
Renal failure
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Renal and urinary disorders
Renal failure acute
|
0.19%
1/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Renal and urinary disorders
Renal injury
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.19%
1/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Reproductive system and breast disorders
Testicular necrosis
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.19%
1/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
3.6%
19/525
|
6.0%
16/268
|
4.9%
13/267
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/525
|
0.75%
2/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnia
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.38%
2/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.19%
1/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary toxicity
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.19%
1/525
|
1.5%
4/268
|
0.37%
1/267
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/525
|
0.00%
0/268
|
0.37%
1/267
|
|
Vascular disorders
Aortic aneurysm
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Vascular disorders
Hypertension
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Vascular disorders
Hypotension
|
0.38%
2/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Vascular disorders
Orthostatic hypotension
|
0.19%
1/525
|
0.00%
0/268
|
0.00%
0/267
|
|
Vascular disorders
Subclavian artery stenosis
|
0.00%
0/525
|
0.37%
1/268
|
0.00%
0/267
|
Other adverse events
| Measure |
Glycopyrronium Bromide 50 μg
n=525 participants at risk
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Placebo to Glycopyrronium Bromide
n=268 participants at risk
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=267 participants at risk
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
1.9%
10/525
|
2.2%
6/268
|
1.9%
5/267
|
|
Gastrointestinal disorders
Dry mouth
|
3.0%
16/525
|
1.9%
5/268
|
1.5%
4/267
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.76%
4/525
|
2.2%
6/268
|
1.1%
3/267
|
|
Gastrointestinal disorders
Nausea
|
1.7%
9/525
|
2.2%
6/268
|
1.5%
4/267
|
|
General disorders
Oedema peripheral
|
1.7%
9/525
|
2.2%
6/268
|
3.0%
8/267
|
|
Infections and infestations
Bronchitis
|
3.6%
19/525
|
3.4%
9/268
|
4.5%
12/267
|
|
Infections and infestations
Lower respiratory tract infection
|
4.2%
22/525
|
3.4%
9/268
|
3.7%
10/267
|
|
Infections and infestations
Nasopharyngitis
|
9.0%
47/525
|
5.6%
15/268
|
7.9%
21/267
|
|
Infections and infestations
Sinusitis
|
5.3%
28/525
|
5.2%
14/268
|
3.4%
9/267
|
|
Infections and infestations
Upper respiratory tract infection
|
10.9%
57/525
|
12.3%
33/268
|
10.9%
29/267
|
|
Infections and infestations
Upper respiratory tract infection bacterial
|
5.3%
28/525
|
9.3%
25/268
|
7.5%
20/267
|
|
Infections and infestations
Urinary tract infection
|
2.7%
14/525
|
3.0%
8/268
|
6.0%
16/267
|
|
Infections and infestations
Viral infection
|
0.19%
1/525
|
2.2%
6/268
|
1.5%
4/267
|
|
Infections and infestations
Viral upper respiratory tract infection
|
1.7%
9/525
|
4.9%
13/268
|
3.4%
9/267
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.9%
10/525
|
2.6%
7/268
|
2.6%
7/267
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.6%
24/525
|
3.4%
9/268
|
4.5%
12/267
|
|
Nervous system disorders
Dizziness
|
1.7%
9/525
|
2.2%
6/268
|
1.9%
5/267
|
|
Nervous system disorders
Headache
|
4.8%
25/525
|
5.2%
14/268
|
4.5%
12/267
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
34.3%
180/525
|
39.6%
106/268
|
31.8%
85/267
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.0%
21/525
|
4.5%
12/268
|
4.5%
12/267
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.7%
14/525
|
4.1%
11/268
|
2.2%
6/267
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.1%
6/525
|
2.2%
6/268
|
0.75%
2/267
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.19%
1/525
|
3.4%
9/268
|
1.5%
4/267
|
|
Vascular disorders
Hypertension
|
3.8%
20/525
|
4.5%
12/268
|
5.2%
14/267
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862 778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER