Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Anticholinergic, Antimuscarinic, Chronic Obstructive Airway Disease, Chronic Obstructive Lung Disease, Chronic Obstructive Pulmonary Disease, COPD, LAMA, Lung Disease, Lung Diseases, Obstructive, Lung Function, Muscarinic receptor antagonist, Pulmonary Disease, Chronic Obstructive, Respiratory Tract Diseases
Brief summary
The study serves to determine whether the treatment of patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with the investigational drug NVA237 is efficient and safe. The efficacy and safety of the drug will be tested against a placebo treatment. The primary criterion to assess efficacy will be the difference between the serial lung function measurements of patients who have been treated for 12 weeks with NVA237 versus those that have received placebo treatment for 12 weeks. A serial lung function measurement (FEV1 testing) will be conducted and the area under the curve will be the measure for the ability to breathe.
Interventions
DRUGNVA237
NVA237 (Glycopyrronioum bromide) as a powder for inhalation in single-dose capsules
DRUGPlacebo
Placebo powder for inhalation in single-dose capsules (matching those for NVA237).
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with airflow obstruction of level 2 and 3 according to the current Global initiative for chronic Obstructive Lung Disease (GOLD) strategy (2011). 2. Patients with Forced Expiratory Volume in one second (FEV1) ≥ 30% and \<80 % of the predicted normal, and FEV1/FVC \< 0.70 when measured 45 min after the inhalation of 84 µg ipratropium bromide. 3\. Current or ex-smokers with at least 10 cigarette pack years smoking history.
Exclusion criteria
1. Patients with a history of long QT syndrome, with a prolonged QTc measured during screening, or patients who have a clinically significant ECG abnormality at screening. 2. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 3. Pregnant or nursing (lactating) women. Women of childbearing potential unless using an effective method of contraception. 4. Patients who in the judgment of the investigator, would be at potential risk if enrolled into the study. 5. Patients who have a clinically significant concomitant disease at screening, including but not limited to clinically significant laboratory abnormalities, clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities, or with uncontrolled diabetes, which could interfere with the assessment of the efficacy and safety of the study treatment. 6. Patients with a body mass index (BMI) of more than 40 kg/m2. 7. Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, long and short acting beta-2 agonists, or sympathomimetic amines. 8. Patients with any history of asthma, with onset of symptoms prior to age 40 years, or patients with a high blood eosinophil count during screening. Other protocol-defnied inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing | Week 12 | The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Day 1 and Week 12 | The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur. |
| Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | Day 1 and week 12 | The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. Time points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur. |
| Mean Trough Forced Expiratory Volume in One Second | Day 1 and week 12 | Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1 |
| Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire | Week 12 | The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline). |
| Breathlessness Assessed by Transition Dyspnea Index | Week 12 | Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1. |
| Change From Baseline in Mean Number of Puffs of Rescue Medication Per Day | Baseline and week 12 | Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication. |
| Change From Baseline in the Percentage of Days Without Rescue Medication Use | Baseline and week 12 | Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the the run-in epoch prior to randomization. |
| Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing | Day 1 | The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. .The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur. |
| Change From Baseline in the Percentage of Nights With no Nighttime Awakenings | Day 1 and week 12 | Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is no waking due to symptoms. A night with no nighttime awakening is defined from diary data as any night where the patient did not wake up due to symptoms. The change from baseline in the percentage of nights with no nighttime awakening is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being The baseline is calculated from the run-in epoch prior to randomization. |
| Change From Baseline in the Percentage of Days With no Daytime Symptoms | Day 1 to week 12 | Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. A day with no daytime symptoms is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours in the evening questionnaire. The change from baseline in the percentage of days with no daytime symptoms is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. The baseline is calculated from the run-in epoch prior to randomization. |
| Change From Baseline in Percentage of Days Able to Perform Usual Daily Activities | Day 1 to week 12 | Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities (Did your respiratory symptoms stop you performing your usual daily activities today). The answer with the lowest symptom score is not at all. A day able to perform usual daily activities is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The change from baseline in the percentage of days able to perform usual daily activities is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe baseline is calculated from the run-in epoch prior to randomization. |
| Change From Baseline in Forced Vital Capacity at All Individual Timepoints | Day 1 and week 12 | The Forced Vital Capacity (FVC)assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur. |
| Change From Baseline in Mean Trough Forced Vital Capacity | Day 1 and week 12 | Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline. |
| Change From Baseline in Morning and Nighttime Symptom Scores | Day 1 to week 12 | Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline. |
| Change From Baseline in Daily Symptom Scores | day 1 to week 12 | Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NVA237 NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks | 216 |
| Placebo Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks | 216 |
| Total | 432 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Patient/guardian decision | 7 | 9 |
Baseline characteristics
| Characteristic | NVA237 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.9 Years STANDARD_DEVIATION 8.55 | 64.2 Years STANDARD_DEVIATION 8.41 | 64.1 Years STANDARD_DEVIATION 8.47 |
| Sex: Female, Male Female | 88 Participants | 90 Participants | 178 Participants |
| Sex: Female, Male Male | 128 Participants | 126 Participants | 254 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 88 / 216 | 81 / 214 |
| serious Total, serious adverse events | 9 / 216 | 5 / 214 |
Outcome results
Primary
Change From Baseline in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur
Time frame: Week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing | 0.115 Liters | Standard Error 0.0153 |
| Placebo | Change From Baseline in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing | -0.008 Liters | Standard Error 0.0153 |
Secondary
Breathlessness Assessed by Transition Dyspnea Index
Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1.
Time frame: Week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Breathlessness Assessed by Transition Dyspnea Index | 0.95 Score | Standard Error 0.28 |
| Placebo | Breathlessness Assessed by Transition Dyspnea Index | 0.48 Score | Standard Error 0.277 |
Secondary
Change From Baseline in Daily Symptom Scores
Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity.
Time frame: day 1 to week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in Daily Symptom Scores | -1.09 Score | Standard Error 0.103 |
| Placebo | Change From Baseline in Daily Symptom Scores | -0.80 Score | Standard Error 0.104 |
Secondary
Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints
The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. Time points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur.
Time frame: Day 1 and week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 5 min (n=207,202) | 4.9 Percent | Standard Deviation 8.67 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 15 min (n=209,201) | 9.9 Percent | Standard Deviation 10.05 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 1 h (n=205,205) | 13.9 Percent | Standard Deviation 11.98 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 2 h (n=201,205) | 16.0 Percent | Standard Deviation 14.42 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 4 h (n=199,202) | 12.7 Percent | Standard Deviation 13.39 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 6h (n=197,197) | 10.3 Percent | Standard Deviation 13.82 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 8 h (n=200,189) | 8.9 Percent | Standard Deviation 14.43 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 11 h 55min (n=184,182) | 6.6 Percent | Standard Deviation 13.44 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, -45min (n=184,188) | 6.4 Percent | Standard Deviation 17.61 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, -15min (n=180,185) | 9.6 Percent | Standard Deviation 18.23 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 5min (n=185,178) | 10.4 Percent | Standard Deviation 18.78 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 15min (n=186,189) | 12.9 Percent | Standard Deviation 20 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 1h (n=184,187) | 15.8 Percent | Standard Deviation 20.49 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 2h (n=178,187) | 16.0 Percent | Standard Deviation 20.83 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 4h (n=179,183) | 12.5 Percent | Standard Deviation 19.72 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 6h (n=174,172) | 9.8 Percent | Standard Deviation 18.78 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 8h (n=178,174) | 7.8 Percent | Standard Deviation 18.18 |
| NVA237 | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 11h 55min (n=171,171) | 7.2 Percent | Standard Deviation 19.39 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 2h (n=178,187) | 2.4 Percent | Standard Deviation 18.52 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 5 min (n=207,202) | -0.3 Percent | Standard Deviation 7.07 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, -15min (n=180,185) | 2.7 Percent | Standard Deviation 17.82 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 15 min (n=209,201) | 0.3 Percent | Standard Deviation 7.62 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 11h 55min (n=171,171) | -2.1 Percent | Standard Deviation 20.07 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 1 h (n=205,205) | 1.2 Percent | Standard Deviation 9.05 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 5min (n=185,178) | 1.8 Percent | Standard Deviation 17.22 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 2 h (n=201,205) | 2.5 Percent | Standard Deviation 9.8 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 4h (n=179,183) | 3.5 Percent | Standard Deviation 20.25 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 4 h (n=199,202) | 2.2 Percent | Standard Deviation 12.63 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 15min (n=186,189) | 2.0 Percent | Standard Deviation 17.08 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 6h (n=197,197) | 2.2 Percent | Standard Deviation 11.88 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 8h (n=178,174) | 0.2 Percent | Standard Deviation 18.86 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 8 h (n=200,189) | -0.5 Percent | Standard Deviation 12.42 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 1h (n=184,187) | 1.6 Percent | Standard Deviation 17.37 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 1, 11 h 55min (n=184,182) | -1.7 Percent | Standard Deviation 14.03 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, 6h (n=174,172) | 2.5 Percent | Standard Deviation 20.84 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints | FEV1, day 85, -45min (n=184,188) | 1.7 Percent | Standard Deviation 17.95 |
Secondary
Change From Baseline in Forced Vital Capacity at All Individual Timepoints
The Forced Vital Capacity (FVC)assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur.
Time frame: Day 1 and week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 5 min (n=214,211) | 0.120 Liters | Standard Error 0.0129 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 15 min (n=214,213) | 0.233 Liters | Standard Error 0.0155 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 1 h (n=215,211) | 0.304 Liters | Standard Error 0.0175 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 2 h (n=211,211) | 0.322 Liters | Standard Error 0.0193 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 4 h (n=209,208) | 0.247 Liters | Standard Error 0.0196 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 6 h (n=208,205) | 0.225 Liters | Standard Error 0.0219 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 8 h (n=209,205) | 0.200 Liters | Standard Error 0.0228 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 11 h 55min (n=203,202) | 0.147 Liters | Standard Error 0.0242 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, -45 min (n=207,204) | 0.123 Liters | Standard Error 0.0248 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, -15 min (n=208,204) | 0.146 Liters | Standard Error 0.0241 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 5 min (n=214,211) | 0.177 Liters | Standard Error 0.0247 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 15 min (n=214,213) | 0.219 Liters | Standard Error 0.0261 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 1 hr (n=215,211) | 0.267 Liters | Standard Error 0.0261 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 2 hr (n=211,211) | 0.275 Liters | Standard Error 0.0277 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 4 hr (n=209,208) | 0.204 Liters | Standard Error 0.0281 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 6 hr (n=208,205) | 0.185 Liters | Standard Error 0.0278 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 8 hr (n=209,205) | 0.152 Liters | Standard Error 0.0264 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 11 hr 55min (n=203,202) | 0.135 Liters | Standard Error 0.029 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 23 hr 15min (n=210,204) | 0.207 Liters | Standard Error 0.0289 |
| NVA237 | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 23 hr 45min (n=213,208) | 0.228 Liters | Standard Error 0.0292 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 11 hr 55min (n=203,202) | -0.045 Liters | Standard Error 0.0288 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 5 min (n=214,211) | -0.014 Liters | Standard Error 0.0131 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 5 min (n=214,211) | 0.001 Liters | Standard Error 0.0251 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 15 min (n=214,213) | 0.005 Liters | Standard Error 0.0157 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 6 hr (n=208,205) | 0.016 Liters | Standard Error 0.0278 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 1 h (n=215,211) | 0.041 Liters | Standard Error 0.0176 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 15 min (n=214,213) | -0.003 Liters | Standard Error 0.0259 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 2 h (n=211,211) | 0.060 Liters | Standard Error 0.0191 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 23 hr 45min (n=213,208) | 0.095 Liters | Standard Error 0.029 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 4 h (n=209,208) | 0.048 Liters | Standard Error 0.0195 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 1 hr (n=215,211) | 0.010 Liters | Standard Error 0.026 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 6 h (n=208,205) | 0.051 Liters | Standard Error 0.022 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 8 hr (n=209,205) | -0.015 Liters | Standard Error 0.0266 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 8 h (n=209,205) | -0.002 Liters | Standard Error 0.0232 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 2 hr (n=211,211) | 0.024 Liters | Standard Error 0.0271 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 1, 11 h 55min (n=203,202) | -0.017 Liters | Standard Error 0.0243 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 23 hr 15min (n=210,204) | 0.066 Liters | Standard Error 0.0284 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, -45 min (n=207,204) | 0.008 Liters | Standard Error 0.0246 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, 4 hr (n=209,208) | 0.035 Liters | Standard Error 0.0278 |
| Placebo | Change From Baseline in Forced Vital Capacity at All Individual Timepoints | FVC, day 85, -15 min (n=208,204) | 0.010 Liters | Standard Error 0.0239 |
Secondary
Change From Baseline in Mean Number of Puffs of Rescue Medication Per Day
Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication.
Time frame: Baseline and week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in Mean Number of Puffs of Rescue Medication Per Day | -1.33 Number of puffs | Standard Error 0.163 |
| Placebo | Change From Baseline in Mean Number of Puffs of Rescue Medication Per Day | -0.80 Number of puffs | Standard Error 0.16 |
Secondary
Change From Baseline in Mean Trough Forced Vital Capacity
Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline.
Time frame: Day 1 and week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Mean Trough Forced Vital Capacity | Day 1 | 0.249 Liters | Standard Error 0.0225 |
| NVA237 | Change From Baseline in Mean Trough Forced Vital Capacity | Week 12 | 0.210 Liters | Standard Error 0.0277 |
| Placebo | Change From Baseline in Mean Trough Forced Vital Capacity | Day 1 | 0.078 Liters | Standard Error 0.0227 |
| Placebo | Change From Baseline in Mean Trough Forced Vital Capacity | Week 12 | 0.080 Liters | Standard Error 0.0276 |
Secondary
Change From Baseline in Morning and Nighttime Symptom Scores
Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline.
Time frame: Day 1 to week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Morning and Nighttime Symptom Scores | Daytime total symptom score (n=207,195) | -0.86 Score | Standard Error 0.097 |
| NVA237 | Change From Baseline in Morning and Nighttime Symptom Scores | Nighttime total symptom score (n=208,200) | -1.03 Score | Standard Error 0.101 |
| Placebo | Change From Baseline in Morning and Nighttime Symptom Scores | Daytime total symptom score (n=207,195) | -0.61 Score | Standard Error 0.1 |
| Placebo | Change From Baseline in Morning and Nighttime Symptom Scores | Nighttime total symptom score (n=208,200) | -0.76 Score | Standard Error 0.102 |
Secondary
Change From Baseline in Percentage of Days Able to Perform Usual Daily Activities
Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities (Did your respiratory symptoms stop you performing your usual daily activities today). The answer with the lowest symptom score is not at all. A day able to perform usual daily activities is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The change from baseline in the percentage of days able to perform usual daily activities is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe baseline is calculated from the run-in epoch prior to randomization.
Time frame: Day 1 to week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in Percentage of Days Able to Perform Usual Daily Activities | 5.2 Percentage of days | Standard Error 1.61 |
| Placebo | Change From Baseline in Percentage of Days Able to Perform Usual Daily Activities | 0.9 Percentage of days | Standard Error 1.65 |
Secondary
Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. .The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.
Time frame: Day 1
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing | 0.121 Liters | Standard Error 0.0096 |
| Placebo | Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing | 0.003 Liters | Standard Error 0.0096 |
Secondary
Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.
Time frame: Day 1 and Week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Day 1 AUC 0-4h (n=215,213) | 0.154 Liters | Standard Error 0.0088 |
| NVA237 | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Week 12 AUC 0-4h (n=215,213) | 0.153 Liters | Standard Error 0.0159 |
| NVA237 | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Day 1 AUC 4-8h (n=213,209) | 0.118 Liters | Standard Error 0.0107 |
| NVA237 | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Week 12 AUC 4-8h (n=213,209) | 0.107 Liters | Standard Error 0.0159 |
| NVA237 | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Day 1 AUC 8-12h (n=212,210) | 0.085 Liters | Standard Error 0.012 |
| NVA237 | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Week 12 AUC 8-12h (n=212,210) | 0.075 Liters | Standard Error 0.0164 |
| Placebo | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Day 1 AUC 8-12h (n=212,210) | -0.021 Liters | Standard Error 0.012 |
| Placebo | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Day 1 AUC 0-4h (n=215,213) | 0.014 Liters | Standard Error 0.0088 |
| Placebo | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Week 12 AUC 4-8h (n=213,209) | 0.000 Liters | Standard Error 0.0158 |
| Placebo | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Week 12 AUC 0-4h (n=215,213) | 0.004 Liters | Standard Error 0.0159 |
| Placebo | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Week 12 AUC 8-12h (n=212,210) | -0.033 Liters | Standard Error 0.0164 |
| Placebo | Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing | Day 1 AUC 4-8h (n=213,209) | 0.011 Liters | Standard Error 0.0109 |
Secondary
Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire
The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).
Time frame: Week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire | -6.4 Score | Standard Error 1.08 |
| Placebo | Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire | -1.2 Score | Standard Error 1.06 |
Secondary
Change From Baseline in the Percentage of Days With no Daytime Symptoms
Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. A day with no daytime symptoms is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours in the evening questionnaire. The change from baseline in the percentage of days with no daytime symptoms is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. The baseline is calculated from the run-in epoch prior to randomization.
Time frame: Day 1 to week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in the Percentage of Days With no Daytime Symptoms | 3.6 Percentage of days | Standard Error 1.17 |
| Placebo | Change From Baseline in the Percentage of Days With no Daytime Symptoms | 2.6 Percentage of days | Standard Error 1.18 |
Secondary
Change From Baseline in the Percentage of Days Without Rescue Medication Use
Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the the run-in epoch prior to randomization.
Time frame: Baseline and week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in the Percentage of Days Without Rescue Medication Use | 11.4 percentage of days | Standard Error 1.95 |
| Placebo | Change From Baseline in the Percentage of Days Without Rescue Medication Use | 7.0 percentage of days | Standard Error 1.97 |
Secondary
Change From Baseline in the Percentage of Nights With no Nighttime Awakenings
Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is no waking due to symptoms. A night with no nighttime awakening is defined from diary data as any night where the patient did not wake up due to symptoms. The change from baseline in the percentage of nights with no nighttime awakening is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being The baseline is calculated from the run-in epoch prior to randomization.
Time frame: Day 1 and week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NVA237 | Change From Baseline in the Percentage of Nights With no Nighttime Awakenings | 13.1 Percentage of nights | Standard Error 1.52 |
| Placebo | Change From Baseline in the Percentage of Nights With no Nighttime Awakenings | 9.2 Percentage of nights | Standard Error 1.54 |
Secondary
Mean Trough Forced Expiratory Volume in One Second
Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1
Time frame: Day 1 and week 12
Population: The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Mean Trough Forced Expiratory Volume in One Second | Day 1 | 0.128 Liters | Standard Error 0.0129 |
| NVA237 | Mean Trough Forced Expiratory Volume in One Second | Week 12 | 0.123 Liters | Standard Error 0.0166 |
| Placebo | Mean Trough Forced Expiratory Volume in One Second | Week 12 | 0.038 Liters | Standard Error 0.0166 |
| Placebo | Mean Trough Forced Expiratory Volume in One Second | Day 1 | 0.021 Liters | Standard Error 0.013 |