Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, NVA237, QAB149, glycopyrronium bromide
Brief summary
The purpose of the study is to provide long term safety data of NVA237. This study will assess the safety and tolerability of a single dose strength of NVA237.
Interventions
DRUGNVA237
NVA237 will be supplied in capsule form in blister packs for use in the Novartis Concept 1 SDDPI
DRUGLong-acting beta 2-agonist (LABA)
QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept 1 SDDPI
DRUGPlacebo
Placebo to match QAB149
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
1. Male or female patients with COPD according to GOLD 2011 who have signed informed consent. 2. Patients with airflow limitation of 30-80% post-bronchodilator FEV1 at run-in. 3. Current or ex-smokers with a smoking history of at least 10 pack years 4. Patients with a mMRC score of at least 2 at run-in.
Exclusion criteria
1. Patients contraindicated for muscarinic antagonist agents and beta-2 agonists 2. Patients with a history of malignancy of any organ system, treated or untreated, within the last five years 3. Patients with narrow-angle glaucoma, BPH or bladder-neck obstruction or moderate-severe renal impairment or urinary retention 4. Patients who had a COPD exacerbation within 6 weeks prior to screening. 5. Patients requiring long term oxygen therapy prescribed for more than 12 hr per day. 6. Patients with a history of asthma. 7. Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to 40 years of age. 8. Patients with a blood eosinophil count of greater than 600 mm/3 during run-in 9. Patients with concomitant pulmonary disease 10. Patients with a history of certain cardiovascular co-morbid conditions 11. Patients with a diagnosis of alpha-1 anti-trypsin deficiency 12. Patients with active pulmonary tuberculosis 13. Patients in the active phase of a pulmonary rehabilitation programme 14. Other protocol-defined inclusion /
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate | 52 weeks | Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52 | -45 min and -15 minutes baseline and at Week 52 | Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1. |
| Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | -45 min and -15 minutes baseline and at Week 52 | Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. |
| Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | -45 min and -15 minutes baseline and at Week 52 | Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1. |
| Time to Treatment Discontinuation | 52 Weeks | Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems |
| Change From Baseline in Mean Daily Number of Puffs of Rescue Medication | 52 weeks | The number of puffs of rescue medication taken in the previous 12 hours was recorded by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect |
| Time to First COPD Exacerbation (Moderate or Severe). | 52 weeks | COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method. |
| Change From Baseline in COPD Symptoms | 52 weeks | The total symptom score was defined as the sum of individual cores for respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and reathlessness. Where a patient had a morning score and an evening score for an individual symptom on one particular day then the worst score was to be taken as the daily score for that symptom. Each symptom scale ranged from 0-3 where 0 was no symptoms and 3 was the worst. The total daily/daytime/nighttime symptom score consists of looking at the score for 6 symptoms and can therefore have a minimum score of 0 or a maximum of 18. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NVA237 12.5 μg twice-daily | 251 |
| QAB149 75 μg once-daily | 256 |
| Total | 507 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 2 |
| Overall Study | Lost to Follow-up | 10 | 7 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol deviation | 1 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 3 |
| Overall Study | Subject/guardian decision | 31 | 35 |
Baseline characteristics
| Characteristic | NVA237 | QAB149 | Total |
|---|---|---|---|
| Age, Continuous | 63.3 Years STANDARD_DEVIATION 9.15 | 63.2 Years STANDARD_DEVIATION 8.91 | 63.3 Years STANDARD_DEVIATION 9.02 |
| Sex: Female, Male Female | 110 Participants | 107 Participants | 217 Participants |
| Sex: Female, Male Male | 141 Participants | 149 Participants | 290 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 165 / 251 | 170 / 256 |
| serious Total, serious adverse events | 33 / 251 | 34 / 256 |
Outcome results
Primary
Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Time frame: 52 weeks
Population: Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with safety assessments were included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVA237 | Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate | 77.3 Percentage of participants |
| QAB149 | Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate | 77 Percentage of participants |
Secondary
Change From Baseline in COPD Symptoms
Percentage of days with 'no daytime symptoms' A day with 'no daytime symptoms' was defined from the diary data as any day where the patient had recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours (approximately 8 am to 8pm). However, a patient was not considered symptom free if they had used rescue medication that day even if his/her total daytime symptoms score was zero. Percentage of nights with 'no nighttime awakenings' A night with 'no nighttime awakenings' was defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the treatment period was divided by the total number of nights where diary recordings had been made in order to derive the percentage nights with 'no nighttime awakenings'.
Time frame: 52 weeks
Population: Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in COPD Symptoms | Nights with no nighttime awakenings (n=226, 222) | 17.4 Percentage of days / nights | Standard Error 1.84 |
| NVA237 | Change From Baseline in COPD Symptoms | Days with no daytime symptoms (n=221, 220) | 6.0 Percentage of days / nights | Standard Error 1.38 |
| NVA237 | Change From Baseline in COPD Symptoms | Days able to perform daily activities(n=221,220) | 5.4 Percentage of days / nights | Standard Error 2.09 |
| QAB149 | Change From Baseline in COPD Symptoms | Nights with no nighttime awakenings (n=226, 222) | 18.0 Percentage of days / nights | Standard Error 1.86 |
| QAB149 | Change From Baseline in COPD Symptoms | Days with no daytime symptoms (n=221, 220) | 5.1 Percentage of days / nights | Standard Error 1.38 |
| QAB149 | Change From Baseline in COPD Symptoms | Days able to perform daily activities(n=221,220) | 8.5 Percentage of days / nights | Standard Error 2.1 |
Secondary
Change From Baseline in COPD Symptoms
The total symptom score was defined as the sum of individual cores for respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and reathlessness. Where a patient had a morning score and an evening score for an individual symptom on one particular day then the worst score was to be taken as the daily score for that symptom. Each symptom scale ranged from 0-3 where 0 was no symptoms and 3 was the worst. The total daily/daytime/nighttime symptom score consists of looking at the score for 6 symptoms and can therefore have a minimum score of 0 or a maximum of 18.
Time frame: 52 weeks
Population: Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in COPD Symptoms | Daily total symptom score (n=231, 227) | -1.18 scores on a scale | Standard Error 0.137 |
| NVA237 | Change From Baseline in COPD Symptoms | Daytime total symptom score (n=221, 220) | -0.95 scores on a scale | Standard Error 0.129 |
| NVA237 | Change From Baseline in COPD Symptoms | Nighttime total symptom score (n=226, 222) | -1.11 scores on a scale | Standard Error 0.126 |
| QAB149 | Change From Baseline in COPD Symptoms | Daily total symptom score (n=231, 227) | -1.47 scores on a scale | Standard Error 0.137 |
| QAB149 | Change From Baseline in COPD Symptoms | Daytime total symptom score (n=221, 220) | -1.14 scores on a scale | Standard Error 0.129 |
| QAB149 | Change From Baseline in COPD Symptoms | Nighttime total symptom score (n=226, 222) | -1.25 scores on a scale | Standard Error 0.128 |
Secondary
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
The number of puffs of rescue medication taken in the previous 12 hours was recorded by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect
Time frame: 52 weeks
Population: Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication | Daily (n=231, 227) | -1.16 Number of puffs | Standard Error 0.199 |
| NVA237 | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication | Daytime (n=221, 220) | -0.71 Number of puffs | Standard Error 0.112 |
| NVA237 | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication | Nighttime (n=226, 222) | -0.52 Number of puffs | Standard Error 0.094 |
| QAB149 | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication | Daily (n=231, 227) | -1.79 Number of puffs | Standard Error 0.199 |
| QAB149 | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication | Daytime (n=221, 220) | -1.05 Number of puffs | Standard Error 0.112 |
| QAB149 | Change From Baseline in Mean Daily Number of Puffs of Rescue Medication | Nighttime (n=226, 222) | -0.73 Number of puffs | Standard Error 0.095 |
Secondary
Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52
Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1.
Time frame: -45 min and -15 minutes baseline and at Week 52
Population: The Full Analysis set (FAS) included patients who received at least one dose of study medication. Patients were analyzed according to the treatment to which they were randomized. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52 | 0.056 Liters | Standard Error 0.0211 |
| QAB149 | Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52 | 0.060 Liters | Standard Error 0.0213 |
Secondary
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1.
Time frame: -45 min and -15 minutes baseline and at Week 52
Population: The Full Analysis set (FAS). At each day/time point, only subjects with a value at both baseline and the respective day/time point are included. Only participants with baseline and specific post baseline time points were included in the analysis for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 141/-15min | 0.096 Liters | Standard Deviation 0.206 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 197/-45min | 0.071 Liters | Standard Deviation 0.237 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 197/-15min | 0.073 Liters | Standard Deviation 0.215 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 29/-45min | 0.104 Liters | Standard Deviation 0.1848 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 253/-45min | 0.092 Liters | Standard Deviation 0.2774 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 85/-45min | 0.105 Liters | Standard Deviation 0.241 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 253/-15min | 0.094 Liters | Standard Deviation 0.21 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 57/-45min | 0.098 Liters | Standard Deviation 0.2017 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 309/-45min | 0.068 Liters | Standard Deviation 0.285 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 85/-15min | 0.111 Liters | Standard Deviation 0.2137 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 309/-15min | 0.088 Liters | Standard Deviation 0.2845 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 29/-15min | 0.123 Liters | Standard Deviation 0.1872 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 365/-45min | 0.057 Liters | Standard Deviation 0.2541 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 141/-45min | 0.071 Liters | Standard Deviation 0.2168 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 365/-15min | 0.087 Liters | Standard Deviation 0.2592 |
| NVA237 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 57/-15min | 0.120 Liters | Standard Deviation 0.2025 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 365/-15min | 0.090 Liters | Standard Deviation 0.2627 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 197/-45min | 0.082 Liters | Standard Deviation 0.2637 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 29/-45min | 0.118 Liters | Standard Deviation 0.2093 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 29/-15min | 0.138 Liters | Standard Deviation 0.2061 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 57/-45min | 0.101 Liters | Standard Deviation 0.2091 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 57/-15min | 0.107 Liters | Standard Deviation 0.2111 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 85/-45min | 0.085 Liters | Standard Deviation 0.2255 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 85/-15min | 0.099 Liters | Standard Deviation 0.2328 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 141/-45min | 0.089 Liters | Standard Deviation 0.2595 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 197/-15min | 0.090 Liters | Standard Deviation 0.2827 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 253/-45min | 0.087 Liters | Standard Deviation 0.2679 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 253/-15min | 0.103 Liters | Standard Deviation 0.2659 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 309/-45min | 0.094 Liters | Standard Deviation 0.2594 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 309/-15min | 0.112 Liters | Standard Deviation 0.2638 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 365/-45min | 0.088 Liters | Standard Deviation 0.2521 |
| QAB149 | Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints | Day 141/-15min | 0.108 Liters | Standard Deviation 0.267 |
Secondary
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1.
Time frame: -45 min and -15 minutes baseline and at Week 52
Population: Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants with baseline and specific post baseline time points were included in the analysis for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 29/-45min | 0.191 Liters | Standard Deviation 0.3433 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 197/-45min | 0.140 Liters | Standard Deviation 0.3879 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 57/-15min | 0.210 Liters | Standard Deviation 0.3414 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 197/-15min | 0.133 Liters | Standard Deviation 0.3992 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 29/-15min | 0.217 Liters | Standard Deviation 0.344 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 253/-45min | 0.167 Liters | Standard Deviation 0.4567 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 253/-15min | 0.153 Liters | Standard Deviation 0.3703 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 85/-15min | 0.188 Liters | Standard Deviation 0.3875 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 309/-45min | 0.120 Liters | Standard Deviation 0.4539 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 85/-45min | 0.171 Liters | Standard Deviation 0.3907 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 309/-15min | 0.149 Liters | Standard Deviation 0.4451 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 141/-45min | 0.159 Liters | Standard Deviation 0.3742 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 365/-45min | 0.116 Liters | Standard Deviation 0.4053 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 57/-45min | 0.168 Liters | Standard Deviation 0.3501 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 365/-15min | 0.143 Liters | Standard Deviation 0.397 |
| NVA237 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 141/-15min | 0.182 Liters | Standard Deviation 0.3706 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 365/-15min | 0.097 Liters | Standard Deviation 0.4171 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 85/-45min | 0.094 Liters | Standard Deviation 0.3711 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 253/-45min | 0.100 Liters | Standard Deviation 0.4219 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 29/-15min | 0.194 Liters | Standard Deviation 0.3495 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 57/-45min | 0.140 Liters | Standard Deviation 0.3655 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 57/-15min | 0.178 Liters | Standard Deviation 0.361 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 85/-15min | 0.118 Liters | Standard Deviation 0.3823 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 141/-45min | 0.112 Liters | Standard Deviation 0.3822 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 141/-15min | 0.141 Liters | Standard Deviation 0.4068 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 197/-45min | 0.075 Liters | Standard Deviation 0.4043 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 197/-15min | 0.083 Liters | Standard Deviation 0.4183 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 253/-15min | 0.125 Liters | Standard Deviation 0.3984 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 309/-45min | 0.094 Liters | Standard Deviation 0.4122 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 309/-15min | 0.114 Liters | Standard Deviation 0.4207 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 365/-45min | 0.109 Liters | Standard Deviation 0.4426 |
| QAB149 | Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints | Day 29/-45min | 0.170 Liters | Standard Deviation 0.3536 |
Secondary
Time to First COPD Exacerbation (Moderate or Severe).
COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method.
Time frame: 52 weeks
Population: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Patients were analyzed according to the treatment to which they were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NVA237 | Time to First COPD Exacerbation (Moderate or Severe). | NA Days |
| QAB149 | Time to First COPD Exacerbation (Moderate or Severe). | NA Days |
Secondary
Time to Treatment Discontinuation
Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems
Time frame: 52 Weeks
Population: The Safety set consisted of all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NVA237 | Time to Treatment Discontinuation | NA Days |
| QAB149 | Time to Treatment Discontinuation | 388 Days |