Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
Brief summary
This study was designed to investigate the efficacy and safety of NVA237, a long-acting muscarinic antagonist, in patients with moderate to severe COPD.
Interventions
DRUGNVA237 12.5 µg once daily
NVA237 12.5 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
DRUGNVA237 25.0 µg once daily
NVA237 25.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
DRUGNVA237 12.5 µg twice daily
NVA237 12.5 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.
DRUGNVA237 50.0 µg once daily
NVA237 50.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
DRUGNVA237 25.0 µg twice daily
NVA237 25.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.
DRUGNVA237 100.0 µg once daily
NVA237 100.0 µg via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
DRUGNVA237 50.0 µg twice daily
NVA237 50.0 µg via dry powder inhaler twice daily for 28 days during either period 1 or during period 2.
DRUGPlacebo to NVA237 once daily
Placebo to NVA237 via dry powder inhaler once daily for 28 days during either period 1 or during period 2.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients age 40 years or more * Diagnosis of Chronic Obstructive Lung Disease (COPD) (moderate to severe as classified by the Global Initiative for COPD (GOLD) Guidelines, 2008 * Smoking history of at least 10 pack-years * Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) \<80% and ≥30% of the predicted normal value * Post-bronchodilator FEV1/Forced Vital Capacity (FVC) \<0.7 * Symptomatic patients, according to daily electronic diary data between visit 2 (Day -8) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to visit 3
Exclusion criteria
* Patients who have had a COPD exacerbation requiring systemic corticosteroids and/or antibiotics and/or hospitalization in the 6 weeks prior to the first visit * Patients who have had a respiratory tract infection within 4 weeks prior to the first visit * Patients with concomitant pulmonary disease * Patients with diabetes Type I or uncontrolled diabetes Type II * Any patient with lung cancer or a history of lung cancer * Patients with a history of certain cardiovascular co-morbid conditions * Patients with a history of asthma or a blood eosinophil count \>600/mm3 or onset of symptoms prior to 40 years * Patients with eczema, known high IgE levels or a known positive skin prick test * Patients participating in the active phase of a pulmonary rehabilitation programme * Patients contraindicated for the treatment with anticholinergics, long and short-acting beta-2 agonists or sympathomimetic amines * Patients with a history of alpha-1 anti-trypsin deficiency * Patients on long term oxygen therapy (\>15hr per day) * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | Day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. The maximal response of incremental once daily and twice daily doses of NVA237 that each dose achieves in relation to the maximal effect of NVA237 on Trough FEV1 was measured at Day 28. FEV1 was measured in response to all doses administered (see Outcome Measure #19). All trough FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All trough FEV1 data are reported as a percentage of the theoretical maximal response. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-24 hours at day 28 of treatment was calculated from measurements taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #20). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | -25 min,-15 min (predose); 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. The Area Under the Curve (AUC) 0-24 hours FEV1 between dosing regimens over the range 20 micrograms to 55 micrograms total daily dose at -25 min,-15 min (predose); 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. AUC 0-24 hours FEV1 was measured in response to all doses administered (12.5 µg q.d., 25.0 µg q.d., 12.5 µg b.i.d., 50 µg q.d., 25 µg b.i.d., 100 µg q.d., 50.0 µg b.i.d., and Placebo; see Outcome Measure # 20), and was used to compute modeled dose-response curves for once-daily and twice-daily regimens separately. The difference between those curves was computed at pre-specified theoretical doses (20 µg, 25 µg, 30 µg, 35 µg, 40 µg, 45 µg, 50 µg, and 55 µg) chosen at points likely to show the largest differences between the once-daily and twice-daily regimens. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours were calculated from measurements taken at: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #21). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 12 hours on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response within different doses/regimens of NVA237 was measured using FEV1 at 12 hours on day 28 of treatment. FEV1 was measured in response to all doses administered (see Outcome Measure #22). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Percentage of the maximal response of NVA237 within different doses/regimens of NVA237 on Peak FEV1 was measured at day 28 of treatment. Peak FEV1 was measured in response to all doses administered (see Outcome Measure #23). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | day 28 | Percentage of the maximal response of NVA237 within different doses/regimens of NVA237 on Forced Vital Capacity (FVC) was measured at day 28 of treatment. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC at day 28 of treatment was measured via spirometry (see Outcome Measure #24). All FVC responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FVC data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Days 1, 7 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on Trough FEV1 was measured on Days 1, 7 and 14. Through FEV1 was measured in response to all doses administered (see Outcome Measure #25). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. |
| Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-24 hours, was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14. FEV1 AUC 0-24 hours was measured on days 1 and 14 of treatment in response to all doses administered (see Outcome Measure #26). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-4 hours was calculated from measurements taken at 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14, in response to all doses administered (see Outcome Measure #27). All AUC FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-8 was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7, and 14. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #28). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses was calculated on FEV1 Area Under the Curve (AUC) 0-12 hours from measurements taken at at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14 in response to all doses administered (see Outcome Measure #29). All AUC FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 on FEV1 Area under the curve (AUC) 12-24 hours was calculated from measurements taken at 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #30). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 at 12 hours was measured on days 1 and 14. FEV1 was measured in response to all doses administered (see Outcome Measure #31). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Days 1, 7, and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Percentage of the maximal response of NVA237 doses on Peak FEV1 was measured on days 1, 7 and 14 of treatment. Peak FEV1 was measured in response to all doses administered (see Outcome Measure #32). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. |
| Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Days 1, 7 and 14 | Percentage of the maximal response of NVA237 Doses on Trough Forced Vital Capacity (FVC) on Days 1, 7 and 14. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Trough FVC was assessed via spirometry. (see Outcome Measure #33). Trough FVC is defined as the mean of the FVC values measured at 23 hours 15 mins and 23 hours 45 mins post-dose. |
| Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline, Weeks 1, 2, 3 and 4 | Mean daily use of rescue medication by treatment and time points. Baseline was defined as the average of the total number of puffs of rescue medication during the week prior to treatment start, divided by the total number of days with non-missing rescue data during that week, then puffs were counted during weeks 1, 2, 3 and 4 postdose. |
| Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1 was measured between dosing regimens (over the range 20 micrograms to 55 micrograms total daily dose) after 28 days of treatment. Mean trough FEV1 was measured in response to all doses administered (12.5 µg q.d., 25.0 µg q.d., 12.5 µg b.i.d., 50 µg q.d., 25 µg b.i.d., 100 µg q.d., 50.0 µg b.i.d., and Placebo; see Outcome Measure # 19), and was used to compute modeled dose-response curves for once-daily and twice-daily regimens separately. The difference between those curves was computed at pre-specified theoretical doses (20 µg, 25 µg, 30 µg, 35 µg, 40 µg, 45 µg, 50 µg, and 55 µg) chosen at points likely to show the largest differences between the once-daily and twice-daily regimens. The theoretical responses to each dosing schedule separately and the difference between the once-daily and twice-daily regimens are represented below. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose). FEV1 AUC was calculated as the sum of trapezoids divided by the length of time. |
| Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 12 hours on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. |
| Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 25 min , 15 min pre-dose, 5 min, 15 min, 1 , 2 ,3 , 4 , 6 , 8 , 10 hours , 11 hour 55 min and 14 hour post-dose on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Measurements were taken at 25 min , 15 min pre-dose, 5 min, 15 min, 1 , 2 ,3 , 4 , 6 , 8 , 10 hours , 11 hour 55 min and 14 hour post-dose on day 28. |
| Trough Forced Vital Capacity After 28 Days of Treatment | 23 hours 15 mins and 23 hours 45 mins post-dose on Day 28 | Forced Vital Capacity (FVC) after 28 days of treatment. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. Trough FVC was defined as the mean of the FVC values measured at 23 hours 15 mins and 23 hours 45 mins post-dose. |
| Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | 23 hours 15 mins and 23 hours 45 mins post-dose on Days 1, 7 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. Trough FEV1 was measured on Days 1, 7 and 14 of treatment. Trough FEV1 was defined as the mean of the FEV1 values measured at 23 hours 15 mins and 23 hours 45 mins post-dose. |
| Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14 of treatment. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time. |
| Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4 hours (postdose) on days 1, 7 and 14 of treatment. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time. |
| Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-8 was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7, and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time. |
| Trough Forced Vital Capacity on Days 1, 7 and 14 | Days 1, 7 and 14 | Trough Forced Vital Capacity (FVC) on Days 1, 7 and 14. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. (see Outcome Measure #23). Trough FVC was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. |
| Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses was calculated on FEV1 Area Under the Curve (AUC) 0-12 hours from measurements taken at at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time. |
| Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 on FEV1 Area under the curve (AUC) 12-24 hours was calculated from measurements taken at 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time. |
| Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Days 1 and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 at 12 hours was measured on days 1 and 14. |
| Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Days 1, 7, and 14 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Percentage of the maximal response of NVA237 doses on Peak FEV1 was measured on days 1, 7 and 14 of treatment. |
| Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time. |
| Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | Day 28 | Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. |
Countries
Belgium, Germany, Hungary, Netherlands, Poland, Spain, United States
Participant flow
Recruitment details
Participants were randomized to 1 of 8 treatment groups during period 1; participants were then switched to a different treatment group during period 2 after a 7 days wash out. Each period lasted up to 29 days.
Pre-assignment details
For this crossover study, a participant is counted in 2 treatment groups
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants in the safety set | 386 |
| Total | 386 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal lab value | 1 |
| Overall Study | Administrative | 2 |
| Overall Study | Adverse Event | 25 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Protocol Violation | 5 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 61.2 Years STANDARD_DEVIATION 7.91 |
| Sex: Female, Male Female | 251 Participants |
| Sex: Female, Male Male | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 89 | 11 / 96 | 5 / 96 | 7 / 92 | 8 / 96 | 9 / 96 | 9 / 87 | 14 / 91 |
| serious Total, serious adverse events | 2 / 89 | 2 / 96 | 1 / 96 | 3 / 92 | 4 / 96 | 3 / 96 | 1 / 87 | 3 / 91 |
Outcome results
Primary
Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. The maximal response of incremental once daily and twice daily doses of NVA237 that each dose achieves in relation to the maximal effect of NVA237 on Trough FEV1 was measured at Day 28. FEV1 was measured in response to all doses administered (see Outcome Measure #19). All trough FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All trough FEV1 data are reported as a percentage of the theoretical maximal response. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.
Time frame: Day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | 27.1 Percentage of maximal response | 90% Confidence Interval 0.454 |
| NVA237 25.0 µg q.d. | Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | 42.0 Percentage of maximal response | 90% Confidence Interval 0.471 |
| NVA237 12.5 µg b.i.d. | Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | 61.6 Percentage of maximal response | 90% Confidence Interval 0.456 |
| NVA237 50.0 µg q.d. | Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | 58.5 Percentage of maximal response | 90% Confidence Interval 0.389 |
| NVA237 25.0 µg b.i.d. | Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | 75.5 Percentage of maximal response | 90% Confidence Interval 0.508 |
| NVA237 100.0 µg q.d. | Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | 73.0 Percentage of maximal response | 90% Confidence Interval 0.512 |
| NVA237 50.0 µg b.i.d. | Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28 | 85.4 Percentage of maximal response | 90% Confidence Interval 0.463 |
Secondary
Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. The Area Under the Curve (AUC) 0-24 hours FEV1 between dosing regimens over the range 20 micrograms to 55 micrograms total daily dose at -25 min,-15 min (predose); 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. AUC 0-24 hours FEV1 was measured in response to all doses administered (12.5 µg q.d., 25.0 µg q.d., 12.5 µg b.i.d., 50 µg q.d., 25 µg b.i.d., 100 µg q.d., 50.0 µg b.i.d., and Placebo; see Outcome Measure # 20), and was used to compute modeled dose-response curves for once-daily and twice-daily regimens separately. The difference between those curves was computed at pre-specified theoretical doses (20 µg, 25 µg, 30 µg, 35 µg, 40 µg, 45 µg, 50 µg, and 55 µg) chosen at points likely to show the largest differences between the once-daily and twice-daily regimens.
Time frame: -25 min,-15 min (predose); 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 20 ug | 0.008 Liters |
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 25 ug | 0.008 Liters |
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 30 ug | 0.008 Liters |
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 35 ug | 0.008 Liters |
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 40 ug | 0.008 Liters |
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 45 ug | 0.008 Liters |
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 50 ug | 0.008 Liters |
| Overall Study | Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment | Total daily dose 55 ug | 0.007 Liters |
Secondary
Mean Daily Use of Rescue Medication by Treatment at Different Time Points
Mean daily use of rescue medication by treatment and time points. Baseline was defined as the average of the total number of puffs of rescue medication during the week prior to treatment start, divided by the total number of days with non-missing rescue data during that week, then puffs were counted during weeks 1, 2, 3 and 4 postdose.
Time frame: Baseline, Weeks 1, 2, 3 and 4
Population: Only patients with a non-missing value at both period baseline and the respective post-baseline visit were included. The modeling approach is not suitable for these data as the modeling assumptions do not hold.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 4.16 Number of Puffs | Standard Deviation 3.131 |
| Overall Study | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 2.91 Number of Puffs | Standard Deviation 2.968 |
| Overall Study | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 2.75 Number of Puffs | Standard Deviation 2.736 |
| Overall Study | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 2.74 Number of Puffs | Standard Deviation 2.784 |
| Overall Study | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.41 Number of Puffs | Standard Deviation 2.338 |
| NVA237 25.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.23 Number of Puffs | Standard Deviation 2.158 |
| NVA237 25.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 2.40 Number of Puffs | Standard Deviation 2.316 |
| NVA237 25.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 2.52 Number of Puffs | Standard Deviation 2.476 |
| NVA237 25.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 2.20 Number of Puffs | Standard Deviation 2.054 |
| NVA237 25.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 4.16 Number of Puffs | Standard Deviation 2.925 |
| NVA237 12.5 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.10 Number of Puffs | Standard Deviation 2.337 |
| NVA237 12.5 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 2.42 Number of Puffs | Standard Deviation 2.773 |
| NVA237 12.5 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 3.83 Number of Puffs | Standard Deviation 3.218 |
| NVA237 12.5 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 2.29 Number of Puffs | Standard Deviation 2.354 |
| NVA237 12.5 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 2.22 Number of Puffs | Standard Deviation 2.541 |
| NVA237 50.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 2.38 Number of Puffs | Standard Deviation 2.541 |
| NVA237 50.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 2.46 Number of Puffs | Standard Deviation 2.504 |
| NVA237 50.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 4.45 Number of Puffs | Standard Deviation 3.068 |
| NVA237 50.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.36 Number of Puffs | Standard Deviation 2.291 |
| NVA237 50.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 2.37 Number of Puffs | Standard Deviation 2.58 |
| NVA237 25.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 2.08 Number of Puffs | Standard Deviation 2.568 |
| NVA237 25.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 3.47 Number of Puffs | Standard Deviation 2.996 |
| NVA237 25.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.13 Number of Puffs | Standard Deviation 2.349 |
| NVA237 25.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 2.23 Number of Puffs | Standard Deviation 2.743 |
| NVA237 25.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 2.32 Number of Puffs | Standard Deviation 2.99 |
| NVA237 100.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 2.59 Number of Puffs | Standard Deviation 2.658 |
| NVA237 100.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 2.75 Number of Puffs | Standard Deviation 2.868 |
| NVA237 100.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.53 Number of Puffs | Standard Deviation 2.609 |
| NVA237 100.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 4.81 Number of Puffs | Standard Deviation 3.276 |
| NVA237 100.0 µg q.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 2.65 Number of Puffs | Standard Deviation 2.828 |
| NVA237 50.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 2.82 Number of Puffs | Standard Deviation 3.003 |
| NVA237 50.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 4.25 Number of Puffs | Standard Deviation 3.613 |
| NVA237 50.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.54 Number of Puffs | Standard Deviation 2.678 |
| NVA237 50.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 2.78 Number of Puffs | Standard Deviation 2.899 |
| NVA237 50.0 µg b.i.d. | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 2.69 Number of Puffs | Standard Deviation 2.977 |
| Placebo | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 4 (n=86, 92, 94, 88, 93, 93, 82, 85) | 3.41 Number of Puffs | Standard Deviation 3.761 |
| Placebo | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 3 (n= 86, 93, 94, 89, 93, 93, 83, 87) | 3.34 Number of Puffs | Standard Deviation 3.66 |
| Placebo | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Baseline (n=89, 95, 95, 92, 96, 96, 86, 91) | 4.62 Number of Puffs | Standard Deviation 3.71 |
| Placebo | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 2 (n=86, 94, 94, 91, 95, 93, 84, 89) | 3.32 Number of Puffs | Standard Deviation 3.455 |
| Placebo | Mean Daily Use of Rescue Medication by Treatment at Different Time Points | Week 1 (n=89, 95, 95, 91, 96, 96, 86, 90) | 2.94 Number of Puffs | Standard Deviation 3.075 |
Secondary
Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-24 hours, was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14. FEV1 AUC 0-24 hours was measured on days 1 and 14 of treatment in response to all doses administered (see Outcome Measure #26). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87) | 38.3 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84) | 28.9 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87) | 55.4 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84) | 44.8 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87) | 59.5 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84) | 49.0 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87) | 71.3 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84) | 61.9 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87) | 74.6 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84) | 65.7 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87) | 83.2 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84) | 76.4 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87) | 85.4 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84) | 79.3 Percentage of maximal response* hours |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses was calculated on FEV1 Area Under the Curve (AUC) 0-12 hours from measurements taken at at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14 in response to all doses administered (see Outcome Measure #29). All AUC FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 49.5 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 41.1 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 66.2 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 58.3 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 58.8 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 50.5 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 79.6 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 73.6 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 74.1 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 67.1 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 88.7 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 84.8 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 85.1 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 80.3 Percentage of maximal response* hours |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-24 hours at day 28 of treatment was calculated from measurements taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #20). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 28.9 Percentage of maximal response * hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 44.8 Percentage of maximal response * hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 49.0 Percentage of maximal response * hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 61.9 Percentage of maximal response * hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 65.7 Percentage of maximal response * hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 76.4 Percentage of maximal response * hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 79.3 Percentage of maximal response * hours |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-4 hours was calculated from measurements taken at 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14, in response to all doses administered (see Outcome Measure #27). All AUC FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84) | 50.8 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85) | 50.8 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86) | 58.4 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85) | 66.9 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86) | 73.2 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84) | 66.9 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84) | 58.9 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86) | 66.1 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85) | 58.9 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85) | 79.7 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86) | 84.1 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84) | 79.7 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85) | 73.7 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86) | 79.1 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84) | 73.7 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86) | 91.1 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84) | 88.3 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85) | 88.3 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84) | 84.4 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85) | 84.4 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86) | 88.0 Percentage of maximal response* hours |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours were calculated from measurements taken at: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #21). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-4h (n=82,90,91,89,92,91,82) | 50.8 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-8h (n=82,90,91,90,92,91,82) | 45.8 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-12h (n=82,90,91,90,92,91,82) | 41.1 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 12-24h (n=82,90,91,89,92,91,81) | 25.6 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 12-24h (n=82,90,91,89,92,91,81) | 40.1 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-12h (n=82,90,91,90,92,91,82) | 58.3 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-4h (n=82,90,91,89,92,91,82) | 66.9 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-8h (n=82,90,91,90,92,91,82) | 62.8 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-12h (n=82,90,91,90,92,91,82) | 50.5 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-8h (n=82,90,91,90,92,91,82) | 55.5 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-4h (n=82,90,91,89,92,91,82) | 58.9 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 12-24h (n=82,90,91,89,92,91,81) | 56.6 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-4h (n=82,90,91,89,92,91,82) | 79.7 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-8h (n=82,90,91,90,92,91,82) | 77.1 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-12h (n=82,90,91,90,92,91,82) | 73.6 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 12-24h (n=82,90,91,89,92,91,81) | 56.4 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-4h (n=82,90,91,89,92,91,82) | 73.7 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 12-24h (n=82,90,91,89,92,91,81) | 71.4 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-8h (n=82,90,91,90,92,91,82) | 71.4 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-12h (n=82,90,91,90,92,91,82) | 67.1 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-8h (n=82,90,91,90,92,91,82) | 87.1 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-4h (n=82,90,91,89,92,91,82) | 88.3 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-12h (n=82,90,91,90,92,91,82) | 84.8 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 12-24h (n=82,90,91,89,92,91,81) | 71.2 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-12h (n=82,90,91,90,92,91,82) | 80.3 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-4h (n=82,90,91,89,92,91,82) | 84.4 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 0-8h (n=82,90,91,90,92,91,82) | 83.3 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28 | AUC 12-24h (n=82,90,91,89,92,91,81) | 82.4 Percentage of maximal response* hours |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response within different doses/regimens of NVA237 was measured using FEV1 at 12 hours on day 28 of treatment. FEV1 was measured in response to all doses administered (see Outcome Measure #22). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: 12 hours on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 27.1 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 42.7 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 35.5 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 59.8 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 52.4 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 74.9 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment | 68.7 Percentage of maximal response |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 at 12 hours was measured on days 1 and 14. FEV1 was measured in response to all doses administered (see Outcome Measure #31). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: Days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83) | 35.1 Percentage of maximal response |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78) | 27.1 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83) | 52.0 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78) | 42.7 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83) | 44.4 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78) | 35.5 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83) | 68.4 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78) | 59.8 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83) | 61.5 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78) | 52.4 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83) | 81.2 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78) | 74.9 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83) | 76.1 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78) | 66.7 Percentage of maximal response |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-8 was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7, and 14. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #28). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 45.8 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85) | 45.8 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 54.2 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85) | 62.8 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 70.3 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 62.8 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 55.5 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 63.6 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85) | 55.5 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85) | 77.1 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 82.6 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 77.1 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85) | 71.4 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 77.8 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 71.4 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 90.5 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 87.1 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85) | 87.1 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 83.3 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85) | 83.3 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87) | 87.5 Percentage of maximal response* hours |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 on FEV1 Area under the curve (AUC) 12-24 hours was calculated from measurements taken at 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14. AUC FEV1 was measured in response to all doses administered (see Outcome Measure #30). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87) | 23.9 Percentage of maximal response* hours |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84) | 25.6 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87) | 37.9 Percentage of maximal response* hours |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84) | 40.1 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87) | 54.4 Percentage of maximal response* hours |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84) | 56.6 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87) | 54.1 Percentage of maximal response* hours |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84) | 56.4 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87) | 69.5 Percentage of maximal response* hours |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84) | 71.4 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87) | 69.3 Percentage of maximal response* hours |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84) | 71.2 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87) | 81.1 Percentage of maximal response* hours |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84) | 82.4 Percentage of maximal response* hours |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment
Percentage of the maximal response of NVA237 within different doses/regimens of NVA237 on Forced Vital Capacity (FVC) was measured at day 28 of treatment. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC at day 28 of treatment was measured via spirometry (see Outcome Measure #24). All FVC responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FVC data are reported as a percentage of the theoretical maximal response.
Time frame: day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | 23.3 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | 37.4 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | 53.6 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | 54.0 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | 69.3 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | 69.7 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment | 81.4 Percentage of maximal response |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Percentage of the maximal response of NVA237 within different doses/regimens of NVA237 on Peak FEV1 was measured at day 28 of treatment. Peak FEV1 was measured in response to all doses administered (see Outcome Measure #23). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 53.3 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 69.2 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 61.1 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 81.5 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 75.6 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 89.6 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 85.8 Percentage of maximal response |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Percentage of the maximal response of NVA237 doses on Peak FEV1 was measured on days 1, 7 and 14 of treatment. Peak FEV1 was measured in response to all doses administered (see Outcome Measure #32). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response.
Time frame: Days 1, 7, and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 53.3 Percentage of maximal response |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85) | 53.3 Percentage of maximal response |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86) | 61.7 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85) | 69.2 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86) | 76.0 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 69.2 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 61.1 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86) | 68.9 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85) | 61.1 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85) | 81.5 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86) | 86.1 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 81.5 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85) | 75.6 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86) | 81.3 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 75.6 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86) | 92.3 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 89.6 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85) | 89.6 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84) | 85.8 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85) | 85.8 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86) | 89.5 Percentage of maximal response |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on Trough FEV1 was measured on Days 1, 7 and 14. Through FEV1 was measured in response to all doses administered (see Outcome Measure #25). All FEV1 responses to active doses were corrected using the placebo response. A modeled dose response curve was fit to the placebo-corrected data, and extrapolated to estimate the maximal response. All FEV1 data are reported as a percentage of the theoretical maximal response. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.
Time frame: Days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81) | 27.1 Percentage of maximal response |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85) | 27.1 Percentage of maximal response |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87) | 28.5 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85) | 42.0 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87) | 43.8 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81) | 42.0 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81) | 61.6 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87) | 63.3 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85) | 61.6 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85) | 58.5 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87) | 60.1 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81) | 58.5 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85) | 75.5 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87) | 76.7 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81) | 75.5 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87) | 74.3 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81) | 73.0 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85) | 73.0 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81) | 85.4 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85) | 85.4 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87) | 86.2 Percentage of maximal response |
Secondary
Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14
Percentage of the maximal response of NVA237 Doses on Trough Forced Vital Capacity (FVC) on Days 1, 7 and 14. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Trough FVC was assessed via spirometry. (see Outcome Measure #33). Trough FVC is defined as the mean of the FVC values measured at 23 hours 15 mins and 23 hours 45 mins post-dose.
Time frame: Days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 23.3 Percentage of maximal response |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 23.3 Percentage of maximal response |
| Overall Study | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87) | 22.8 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 37.4 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87) | 36.8 Percentage of maximal response |
| NVA237 25.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 37.4 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 53.6 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87) | 52.9 Percentage of maximal response |
| NVA237 12.5 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 53.6 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 54.0 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87) | 53.4 Percentage of maximal response |
| NVA237 50.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 54.0 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 69.3 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87) | 68.7 Percentage of maximal response |
| NVA237 25.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 69.3 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87) | 69.1 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 69.7 Percentage of maximal response |
| NVA237 100.0 µg q.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 69.7 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 81.4 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 81.4 Percentage of maximal response |
| NVA237 50.0 µg b.i.d. | Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87) | 81.0 Percentage of maximal response |
Secondary
Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1 was measured between dosing regimens (over the range 20 micrograms to 55 micrograms total daily dose) after 28 days of treatment. Mean trough FEV1 was measured in response to all doses administered (12.5 µg q.d., 25.0 µg q.d., 12.5 µg b.i.d., 50 µg q.d., 25 µg b.i.d., 100 µg q.d., 50.0 µg b.i.d., and Placebo; see Outcome Measure # 19), and was used to compute modeled dose-response curves for once-daily and twice-daily regimens separately. The difference between those curves was computed at pre-specified theoretical doses (20 µg, 25 µg, 30 µg, 35 µg, 40 µg, 45 µg, 50 µg, and 55 µg) chosen at points likely to show the largest differences between the once-daily and twice-daily regimens. The theoretical responses to each dosing schedule separately and the difference between the once-daily and twice-daily regimens are represented below.
Time frame: day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 20 ug | 0.037 Liters |
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 25 ug | 0.037 Liters |
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 30 ug | 0.036 Liters |
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 35 ug | 0.035 Liters |
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 40 ug | 0.034 Liters |
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 45 ug | 0.033 Liters |
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 50 ug | 0.032 Liters |
| Overall Study | Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237 | Total daily dose 55 ug | 0.031 Liters |
Other Pre-specified
Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses was calculated on FEV1 Area Under the Curve (AUC) 0-12 hours from measurements taken at at 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.
Time frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.382 Liters | Standard Deviation 0.488 |
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.360 Liters | Standard Deviation 0.447 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.425 Liters | Standard Deviation 0.465 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.416 Liters | Standard Deviation 0.445 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.379 Liters | Standard Deviation 0.474 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.357 Liters | Standard Deviation 0.452 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.430 Liters | Standard Deviation 0.421 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.406 Liters | Standard Deviation 0.388 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.364 Liters | Standard Deviation 0.47 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.378 Liters | Standard Deviation 0.48 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.431 Liters | Standard Deviation 0.544 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.427 Liters | Standard Deviation 0.503 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.494 Liters | Standard Deviation 0.472 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.498 Liters | Standard Deviation 0.484 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.289 Liters | Standard Deviation 0.482 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.281 Liters | Standard Deviation 0.493 |
Other Pre-specified
Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.
Time frame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.307 Liters | Standard Deviation 0.469 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.351 Liters | Standard Deviation 0.392 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.321 Liters | Standard Deviation 0.469 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.317 Liters | Standard Deviation 0.39 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.339 Liters | Standard Deviation 0.462 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.395 Liters | Standard Deviation 0.496 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.457 Liters | Standard Deviation 0.453 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment | 1.247 Liters | Standard Deviation 0.467 |
Other Pre-specified
Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14 of treatment. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.
Time frame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.318 Liters | Standard Deviation 0.47 |
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.306 Liters | Standard Deviation 0.427 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.370 Liters | Standard Deviation 0.444 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.353 Liters | Standard Deviation 0.42 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.354 Liters | Standard Deviation 0.462 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.324 Liters | Standard Deviation 0.43 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.361 Liters | Standard Deviation 0.393 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.348 Liters | Standard Deviation 0.372 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.336 Liters | Standard Deviation 0.46 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.335 Liters | Standard Deviation 0.46 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.376 Liters | Standard Deviation 0.526 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.386 Liters | Standard Deviation 0.493 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.449 Liters | Standard Deviation 0.453 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.466 Liters | Standard Deviation 0.471 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 1 (n= 89,94,93,92,96,96,87,90) | 1.256 Liters | Standard Deviation 0.469 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment | Day 14 (n= 86,92,91,91,95,93,84,86) | 1.253 Liters | Standard Deviation 0.473 |
Other Pre-specified
Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at 5 min, 15 min, 1,2,3,4 hours (postdose) on days 1, 7 and 14 of treatment. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.
Time frame: 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.428 Liters | Standard Deviation 0.492 |
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.451 Liters | Standard Deviation 0.456 |
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.403 Liters | Standard Deviation 0.468 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.473 Liters | Standard Deviation 0.456 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.483 Liters | Standard Deviation 0.463 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.483 Liters | Standard Deviation 0.485 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.390 Liters | Standard Deviation 0.471 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.421 Liters | Standard Deviation 0.489 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.397 Liters | Standard Deviation 0.478 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.469 Liters | Standard Deviation 0.428 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.432 Liters | Standard Deviation 0.407 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.468 Liters | Standard Deviation 0.409 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.390 Liters | Standard Deviation 0.472 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.411 Liters | Standard Deviation 0.483 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.429 Liters | Standard Deviation 0.503 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.453 Liters | Standard Deviation 0.505 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.453 Liters | Standard Deviation 0.551 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.460 Liters | Standard Deviation 0.514 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.537 Liters | Standard Deviation 0.494 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.533 Liters | Standard Deviation 0.501 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.545 Liters | Standard Deviation 0.485 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 1 (n=89,94,93,91,96,96,86,89) | 1.312 Liters | Standard Deviation 0.494 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 7 (n=87,93,90,92,95,94,85,89) | 1.310 Liters | Standard Deviation 0.491 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment | Day 14 (n=86,92,91,91,95,93,84,86) | 1.314 Liters | Standard Deviation 0.5 |
Other Pre-specified
Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours)
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. FEV1 Area Under the Curve (AUC) measurements were taken at: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose). FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.
Time frame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.415 Liters | Standard Deviation 0.494 |
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.386 Liters | Standard Deviation 0.477 |
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.364 Liters | Standard Deviation 0.48 |
| Overall Study | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.251 Liters | Standard Deviation 0.464 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.287 Liters | Standard Deviation 0.382 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.447 Liters | Standard Deviation 0.423 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.478 Liters | Standard Deviation 0.439 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.416 Liters | Standard Deviation 0.416 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.414 Liters | Standard Deviation 0.489 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.280 Liters | Standard Deviation 0.458 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.392 Liters | Standard Deviation 0.491 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.362 Liters | Standard Deviation 0.487 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.431 Liters | Standard Deviation 0.411 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.397 Liters | Standard Deviation 0.411 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.377 Liters | Standard Deviation 0.408 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.264 Liters | Standard Deviation 0.378 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.299 Liters | Standard Deviation 0.459 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.375 Liters | Standard Deviation 0.469 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.397 Liters | Standard Deviation 0.476 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.417 Liters | Standard Deviation 0.487 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.350 Liters | Standard Deviation 0.48 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.442 Liters | Standard Deviation 0.515 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.461 Liters | Standard Deviation 0.52 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.490 Liters | Standard Deviation 0.532 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.421 Liters | Standard Deviation 0.426 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.553 Liters | Standard Deviation 0.504 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.505 Liters | Standard Deviation 0.48 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.527 Liters | Standard Deviation 0.495 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-8h (n=82,90,91,90,92,91,82,82) | 1.305 Liters | Standard Deviation 0.485 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-12h (n=82,90,91,90,92,91,82,82) | 1.285 Liters | Standard Deviation 0.476 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 12-24h (n=82,90,91,89,92,91,81,82) | 1.208 Liters | Standard Deviation 0.461 |
| Placebo | Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) | AUC 0-4h (n=82,90,91,89,92,91,82,82) | 1.315 Liters | Standard Deviation 0.49 |
Other Pre-specified
Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards.
Time frame: 12 hours on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.272 Liters | Standard Deviation 0.471 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.330 Liters | Standard Deviation 0.415 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.279 Liters | Standard Deviation 0.476 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.330 Liters | Standard Deviation 0.384 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.320 Liters | Standard Deviation 0.466 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.391 Liters | Standard Deviation 0.498 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.429 Liters | Standard Deviation 0.449 |
| Placebo | Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment | 1.256 Liters | Standard Deviation 0.472 |
Other Pre-specified
Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 at 12 hours was measured on days 1 and 14.
Time frame: Days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.319 Liters | Standard Deviation 0.502 |
| Overall Study | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.290 Liters | Standard Deviation 0.431 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.364 Liters | Standard Deviation 0.452 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.356 Liters | Standard Deviation 0.431 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.327 Liters | Standard Deviation 0.465 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.303 Liters | Standard Deviation 0.428 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.345 Liters | Standard Deviation 0.405 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.329 Liters | Standard Deviation 0.368 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.299 Liters | Standard Deviation 0.457 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.329 Liters | Standard Deviation 0.455 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.374 Liters | Standard Deviation 0.549 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.389 Liters | Standard Deviation 0.506 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.469 Liters | Standard Deviation 0.436 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.439 Liters | Standard Deviation 0.459 |
| Placebo | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 1 (n=83, 90, 91, 85, 89, 90, 83, 81) | 1.244 Liters | Standard Deviation 0.449 |
| Placebo | Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment | Day 14 (n=84, 91, 88, 90, 90, 92, 78, 83) | 1.268 Liters | Standard Deviation 0.477 |
Other Pre-specified
Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 doses on FEV1 Area Under the Curve (AUC) 0-8 was calculated from measurements taken at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7, and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.
Time frame: at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.381 Liters | Standard Deviation 0.453 |
| Overall Study | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.400 Liters | Standard Deviation 0.486 |
| Overall Study | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.386 Liters | Standard Deviation 0.471 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.450 Liters | Standard Deviation 0.476 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.462 Liters | Standard Deviation 0.455 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.441 Liters | Standard Deviation 0.452 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.375 Liters | Standard Deviation 0.464 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.401 Liters | Standard Deviation 0.483 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.375 Liters | Standard Deviation 0.463 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.409 Liters | Standard Deviation 0.397 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.451 Liters | Standard Deviation 0.426 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.435 Liters | Standard Deviation 0.398 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.390 Liters | Standard Deviation 0.476 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.400 Liters | Standard Deviation 0.486 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.373 Liters | Standard Deviation 0.47 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.433 Liters | Standard Deviation 0.503 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.442 Liters | Standard Deviation 0.508 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.446 Liters | Standard Deviation 0.548 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.519 Liters | Standard Deviation 0.493 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.516 Liters | Standard Deviation 0.481 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.514 Liters | Standard Deviation 0.479 |
| Placebo | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 7 (n= 87, 93, 91, 92, 95, 94, 85, 89) | 1.293 Liters | Standard Deviation 0.489 |
| Placebo | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 1 (n=89, 94, 93, 91, 96, 96, 87, 90) | 1.301 Liters | Standard Deviation 0.488 |
| Placebo | Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14 | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.293 Liters | Standard Deviation 0.498 |
Other Pre-specified
Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Percentage of the maximal response of NVA237 on FEV1 Area under the curve (AUC) 12-24 hours was calculated from measurements taken at 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14. FEV1 AUC was calculated as the sum of trapezoids divided by the length of time.
Time frame: 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.257 Liters | Standard Deviation 0.459 |
| Overall Study | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.251 Liters | Standard Deviation 0.417 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.315 Liters | Standard Deviation 0.432 |
| NVA237 25.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.289 Liters | Standard Deviation 0.405 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.329 Liters | Standard Deviation 0.455 |
| NVA237 12.5 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.290 Liters | Standard Deviation 0.415 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.295 Liters | Standard Deviation 0.375 |
| NVA237 50.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.291 Liters | Standard Deviation 0.366 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.306 Liters | Standard Deviation 0.454 |
| NVA237 25.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.291 Liters | Standard Deviation 0.45 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.322 Liters | Standard Deviation 0.512 |
| NVA237 100.0 µg q.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.344 Liters | Standard Deviation 0.488 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.406 Liters | Standard Deviation 0.437 |
| NVA237 50.0 µg b.i.d. | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.437 Liters | Standard Deviation 0.461 |
| Placebo | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 1 (n=89, 94, 93, 92, 96, 96, 87, 90) | 1.224 Liters | Standard Deviation 0.459 |
| Placebo | Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment | Day 14 (n= 86, 92, 91, 91, 95, 93, 84, 86) | 1.225 Liters | Standard Deviation 0.459 |
Other Pre-specified
Peak Forced Expiratory Volume in One Second at Day 28 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Measurements were taken at 25 min , 15 min pre-dose, 5 min, 15 min, 1 , 2 ,3 , 4 , 6 , 8 , 10 hours , 11 hour 55 min and 14 hour post-dose on day 28.
Time frame: 25 min , 15 min pre-dose, 5 min, 15 min, 1 , 2 ,3 , 4 , 6 , 8 , 10 hours , 11 hour 55 min and 14 hour post-dose on day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.500 Liters | Standard Deviation 0.516 |
| NVA237 25.0 µg q.d. | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.563 Liters | Standard Deviation 0.453 |
| NVA237 12.5 µg b.i.d. | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.494 Liters | Standard Deviation 0.507 |
| NVA237 50.0 µg q.d. | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.514 Liters | Standard Deviation 0.432 |
| NVA237 25.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.504 Liters | Standard Deviation 0.516 |
| NVA237 100.0 µg q.d. | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.570 Liters | Standard Deviation 0.546 |
| NVA237 50.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.630 Liters | Standard Deviation 0.513 |
| Placebo | Peak Forced Expiratory Volume in One Second at Day 28 of Treatment | 1.397 Liters | Standard Deviation 0.515 |
Other Pre-specified
Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Peak FEV1 is the maximum FEV1 recorded in a pre-determined period of time. Percentage of the maximal response of NVA237 doses on Peak FEV1 was measured on days 1, 7 and 14 of treatment.
Time frame: Days 1, 7, and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.503 Liters | Standard Deviation 0.515 |
| Overall Study | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.487 Liters | Standard Deviation 0.471 |
| Overall Study | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.459 Liters | Standard Deviation 0.477 |
| NVA237 25.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.547 Liters | Standard Deviation 0.465 |
| NVA237 25.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.540 Liters | Standard Deviation 0.474 |
| NVA237 25.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.558 Liters | Standard Deviation 0.497 |
| NVA237 12.5 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.465 Liters | Standard Deviation 0.484 |
| NVA237 12.5 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.494 Liters | Standard Deviation 0.507 |
| NVA237 12.5 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.455 Liters | Standard Deviation 0.496 |
| NVA237 50.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.541 Liters | Standard Deviation 0.442 |
| NVA237 50.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.501 Liters | Standard Deviation 0.426 |
| NVA237 50.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.537 Liters | Standard Deviation 0.429 |
| NVA237 25.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.448 Liters | Standard Deviation 0.491 |
| NVA237 25.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.483 Liters | Standard Deviation 0.495 |
| NVA237 25.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.506 Liters | Standard Deviation 0.513 |
| NVA237 100.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.513 Liters | Standard Deviation 0.524 |
| NVA237 100.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.521 Liters | Standard Deviation 0.567 |
| NVA237 100.0 µg q.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.528 Liters | Standard Deviation 0.529 |
| NVA237 50.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.598 Liters | Standard Deviation 0.51 |
| NVA237 50.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.597 Liters | Standard Deviation 0.51 |
| NVA237 50.0 µg b.i.d. | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.615 Liters | Standard Deviation 0.497 |
| Placebo | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 1 (n=89, 94, 93, 91, 96, 96, 86, 89) | 1.378 Liters | Standard Deviation 0.504 |
| Placebo | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 7 (n=87, 93, 90, 92, 95, 94, 85, 89) | 1.364 Liters | Standard Deviation 0.504 |
| Placebo | Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment | Day 14 (n=86, 92, 91, 91, 95, 93, 84, 86) | 1.380 Liters | Standard Deviation 0.509 |
Other Pre-specified
Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. Trough FEV1 was measured on Days 1, 7 and 14 of treatment. Trough FEV1 was defined as the mean of the FEV1 values measured at 23 hours 15 mins and 23 hours 45 mins post-dose.
Time frame: 23 hours 15 mins and 23 hours 45 mins post-dose on Days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.299 Liters | Standard Deviation 0.49 |
| Overall Study | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.336 Liters | Standard Deviation 0.442 |
| Overall Study | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.332 Liters | Standard Deviation 0.499 |
| NVA237 25.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.349 Liters | Standard Deviation 0.446 |
| NVA237 25.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.422 Liters | Standard Deviation 0.432 |
| NVA237 25.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.387 Liters | Standard Deviation 0.477 |
| NVA237 12.5 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.335 Liters | Standard Deviation 0.444 |
| NVA237 12.5 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.375 Liters | Standard Deviation 0.477 |
| NVA237 12.5 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.349 Liters | Standard Deviation 0.467 |
| NVA237 50.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.371 Liters | Standard Deviation 0.406 |
| NVA237 50.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.391 Liters | Standard Deviation 0.392 |
| NVA237 50.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.356 Liters | Standard Deviation 0.391 |
| NVA237 25.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.375 Liters | Standard Deviation 0.486 |
| NVA237 25.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.355 Liters | Standard Deviation 0.503 |
| NVA237 25.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.359 Liters | Standard Deviation 0.479 |
| NVA237 100.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.372 Liters | Standard Deviation 0.501 |
| NVA237 100.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.367 Liters | Standard Deviation 0.514 |
| NVA237 100.0 µg q.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.375 Liters | Standard Deviation 0.519 |
| NVA237 50.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.480 Liters | Standard Deviation 0.474 |
| NVA237 50.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.492 Liters | Standard Deviation 0.483 |
| NVA237 50.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.500 Liters | Standard Deviation 0.455 |
| Placebo | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 1 (n= 88,92,91, 90, 94, 94, 87, 86) | 1.290 Liters | Standard Deviation 0.471 |
| Placebo | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 7 (n= 87,92,90, 91, 95, 93, 85, 87) | 1.294 Liters | Standard Deviation 0.491 |
| Placebo | Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14 | Day 14 (n= 85,90,91, 88, 94, 93, 81, 84) | 1.284 Liters | Standard Deviation 0.471 |
Other Pre-specified
Trough Forced Expiratory Volume in One Second by Treatment at Day 28
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.
Time frame: Day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.319 Liters | Standard Deviation 0.505 |
| NVA237 25.0 µg q.d. | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.368 Liters | Standard Deviation 0.436 |
| NVA237 12.5 µg b.i.d. | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.354 Liters | Standard Deviation 0.484 |
| NVA237 50.0 µg q.d. | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.340 Liters | Standard Deviation 0.4 |
| NVA237 25.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.384 Liters | Standard Deviation 0.472 |
| NVA237 100.0 µg q.d. | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.410 Liters | Standard Deviation 0.522 |
| NVA237 50.0 µg b.i.d. | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.493 Liters | Standard Deviation 0.449 |
| Placebo | Trough Forced Expiratory Volume in One Second by Treatment at Day 28 | 1.268 Liters | Standard Deviation 0.483 |
Other Pre-specified
Trough Forced Vital Capacity After 28 Days of Treatment
Forced Vital Capacity (FVC) after 28 days of treatment. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. Trough FVC was defined as the mean of the FVC values measured at 23 hours 15 mins and 23 hours 45 mins post-dose.
Time frame: 23 hours 15 mins and 23 hours 45 mins post-dose on Day 28
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Trough Forced Vital Capacity After 28 Days of Treatment | 2.939 Liters | Standard Deviation 0.878 |
| NVA237 25.0 µg q.d. | Trough Forced Vital Capacity After 28 Days of Treatment | 3.007 Liters | Standard Deviation 0.91 |
| NVA237 12.5 µg b.i.d. | Trough Forced Vital Capacity After 28 Days of Treatment | 2.954 Liters | Standard Deviation 0.849 |
| NVA237 50.0 µg q.d. | Trough Forced Vital Capacity After 28 Days of Treatment | 2.973 Liters | Standard Deviation 0.825 |
| NVA237 25.0 µg b.i.d. | Trough Forced Vital Capacity After 28 Days of Treatment | 3.041 Liters | Standard Deviation 0.77 |
| NVA237 100.0 µg q.d. | Trough Forced Vital Capacity After 28 Days of Treatment | 2.974 Liters | Standard Deviation 0.999 |
| NVA237 50.0 µg b.i.d. | Trough Forced Vital Capacity After 28 Days of Treatment | 3.080 Liters | Standard Deviation 0.913 |
| Placebo | Trough Forced Vital Capacity After 28 Days of Treatment | 2.703 Liters | Standard Deviation 0.857 |
Other Pre-specified
Trough Forced Vital Capacity on Days 1, 7 and 14
Trough Forced Vital Capacity (FVC) on Days 1, 7 and 14. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. (see Outcome Measure #23). Trough FVC was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values.
Time frame: Days 1, 7 and 14
Population: Full analysis set includes all randomized patients who received at least one dose of study drug and data available for analysis. Only patients with non-missing values were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 2.895 Liters | Standard Deviation 0.83 |
| Overall Study | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 2.958 Liters | Standard Deviation 0.772 |
| Overall Study | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 2.982 Liters | Standard Deviation 0.833 |
| NVA237 25.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 3.000 Liters | Standard Deviation 0.934 |
| NVA237 25.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 3.135 Liters | Standard Deviation 0.928 |
| NVA237 25.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 3.063 Liters | Standard Deviation 0.967 |
| NVA237 12.5 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 2.965 Liters | Standard Deviation 0.862 |
| NVA237 12.5 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 2.997 Liters | Standard Deviation 0.835 |
| NVA237 12.5 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 2.991 Liters | Standard Deviation 0.873 |
| NVA237 50.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 3.017 Liters | Standard Deviation 0.82 |
| NVA237 50.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 3.072 Liters | Standard Deviation 0.833 |
| NVA237 50.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 3.003 Liters | Standard Deviation 0.812 |
| NVA237 25.0 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 2.993 Liters | Standard Deviation 0.798 |
| NVA237 25.0 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 2.956 Liters | Standard Deviation 0.81 |
| NVA237 25.0 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 2.960 Liters | Standard Deviation 0.763 |
| NVA237 100.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 2.977 Liters | Standard Deviation 0.987 |
| NVA237 100.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 2.944 Liters | Standard Deviation 1.001 |
| NVA237 100.0 µg q.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 2.941 Liters | Standard Deviation 0.987 |
| NVA237 50.0 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 3.114 Liters | Standard Deviation 0.975 |
| NVA237 50.0 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 3.088 Liters | Standard Deviation 0.961 |
| NVA237 50.0 µg b.i.d. | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 3.113 Liters | Standard Deviation 0.941 |
| Placebo | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 1 (n=88, 92, 91, 90, 94, 94, 87, 86) | 2.779 Liters | Standard Deviation 0.838 |
| Placebo | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 7 (n=87, 92, 90, 91, 95, 93, 85, 87) | 2.759 Liters | Standard Deviation 0.875 |
| Placebo | Trough Forced Vital Capacity on Days 1, 7 and 14 | Day 14 (n= 85, 90, 91, 88, 94, 93, 81, 84) | 2.744 Liters | Standard Deviation 0.841 |