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 (glycopyrronium 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/ Forced Vital Capacity (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-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing | 12 weeks | The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | Day 1 and Week 12 (Day 85) | The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans 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 time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans. |
| 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). |
| Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at Week 12 | Week 12 | The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). 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 significant improvement in SGRQ is defined as less than or equal to -4 change from baseline. |
| Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12 | Week 12 | Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. |
| Change From Baseline of Daily Symptom Scores | 12 weeks | Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least & 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am & pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day & night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day & night scores. |
| Change From Baseline of Morning and Nighttime Symptom Scores at Week 12 | 12 weeks | Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am & each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least & 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day & night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day & night scores. |
| Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough) | Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose |
| Percentage of Days With no Daytime Symptoms | from Baseline up to 12 weeks | Patients are reporting symptoms by using an electronic diary. 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. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100. |
| Percentage of Days Able to Perform Usual Daily Activities | from Baseline up to 12 weeks | Patients are reporting symptoms by using an electronic diary. 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 Average Number of Puffs of Rescue Medication Per Day | baseline and 12 weeks | Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the mean daily number of puffs used per patient over the 12 weeks treatment period. |
| Percentage of Days Without Rescue Medication Use | 12 weeks | Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization. |
| Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | Baseline, Day 1 and Week 12 (Day 85) | The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed. |
| Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | Baseline, Day 1 and Week 12 (Day 85) | 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. |
| Percentage of Nights With no Nighttime Awakenings | from Baseline up to 12 weeks | Patients are reporting symptoms by using an electronic diary. A night with no nighttime awakening is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks. |
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 | 222 |
| Placebo Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks. | 219 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | non-compliance with study treatment | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | subject/guardian decision | 5 | 6 |
Baseline characteristics
| Characteristic | NVA237 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 8.36 | 62.1 years STANDARD_DEVIATION 8.34 | 62.4 years STANDARD_DEVIATION 8.34 |
| Sex: Female, Male Female | 98 Participants | 87 Participants | 185 Participants |
| Sex: Female, Male Male | 124 Participants | 132 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 72 / 222 | 66 / 216 |
| serious Total, serious adverse events | 11 / 222 | 12 / 216 |
Outcome results
Primary
Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.
Time frame: 12 weeks
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 of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing | 0.125 liters*hr | Standard Error 0.0162 |
| Placebo | Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing | -0.014 liters*hr | Standard Error 0.0165 |
Secondary
Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12
Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.
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 (TDI) Focal Score at Week 12 | 1.46 scores on a scale | Standard Error 0.289 |
| Placebo | Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12 | 0.54 scores on a scale | Standard Error 0.286 |
Secondary
Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans 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 time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans.
Time frame: Day 1 and Week 12 (Day 85)
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 FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 0-4h Day 85 (n=222, n=216) | 0.171 liters*hr | Standard Error 0.0163 |
| NVA237 | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 4-8h Day 85 (n=222, n=215) | 0.115 liters*hr | Standard Error 0.0172 |
| NVA237 | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 0-4h Day 1 (n=222, n=216) | 0.174 liters*hr | Standard Error 0.0103 |
| NVA237 | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 8-12h Day 1 (n=222, n=215) | 0.102 liters*hr | Standard Error 0.0122 |
| NVA237 | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 4-8h Day 1 (n=222, n=215) | 0.138 liters*hr | Standard Error 0.0123 |
| NVA237 | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 8-12h Day 85 (n=222, n=215) | 0.074 liters*hr | Standard Error 0.0166 |
| NVA237 | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 0-12h Day 1 (n=222, n=216) | 0.140 liters*hr | Standard Error 0.0108 |
| Placebo | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 8-12h Day 85 (n=222, n=215) | -0.034 liters*hr | Standard Error 0.0168 |
| Placebo | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 0-12h Day 1 (n=222, n=216) | -0.001 liters*hr | Standard Error 0.0106 |
| Placebo | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 0-4h Day 1 (n=222, n=216) | 0.021 liters*hr | Standard Error 0.0101 |
| Placebo | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 0-4h Day 85 (n=222, n=216) | 0.001 liters*hr | Standard Error 0.0167 |
| Placebo | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 4-8h Day 1 (n=222, n=215) | 0.001 liters*hr | Standard Error 0.0121 |
| Placebo | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 4-8h Day 85 (n=222, n=215) | -0.017 liters*hr | Standard Error 0.0174 |
| Placebo | Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85) | FEV1, AUC 8-12h Day 1 (n=222, n=215) | -0.037 liters*hr | Standard Error 0.012 |
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 | -4.4 score | Standard Error 0.96 |
| Placebo | Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire | -1.7 score | Standard Error 0.96 |
Secondary
Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose
Time frame: Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)
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 | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Trough FEV1 Day 2 (n=218, n=214) | 0.141 liters | Standard Error 0.0124 |
| NVA237 | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Trough FEV1 Day 86 (n=218, n=214) | 0.123 liters | Standard Error 0.0171 |
| NVA237 | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 15 (n=217, n=208) | 0.112 liters | Standard Error 0.0135 |
| NVA237 | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 29 (n=217, n=208) | 0.0105 liters | Standard Error 0.0137 |
| NVA237 | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 57 (n=217, n=208) | 0.0106 liters | Standard Error 0.0156 |
| NVA237 | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 85 (n=217, n=208) | 0.090 liters | Standard Error 0.0155 |
| Placebo | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 57 (n=217, n=208) | -0.006 liters | Standard Error 0.0157 |
| Placebo | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Trough FEV1 Day 2 (n=218, n=214) | 0.025 liters | Standard Error 0.0122 |
| Placebo | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 29 (n=217, n=208) | -0.005 liters | Standard Error 0.0136 |
| Placebo | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Trough FEV1 Day 86 (n=218, n=214) | 0.007 liters | Standard Error 0.0173 |
| Placebo | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 85 (n=217, n=208) | -0.029 liters | Standard Error 0.0157 |
| Placebo | Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit | Pre-dose Trough FEV1 Day 15 (n=217, n=208) | -0.002 liters | Standard Error 0.0135 |
Secondary
Change From Baseline of Daily Symptom Scores
Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least & 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am & pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day & night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day & night scores.
Time frame: 12 weeks
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 of Daily Symptom Scores | -1.39 Score | Standard Error 0.139 |
| Placebo | Change From Baseline of Daily Symptom Scores | -1.01 Score | Standard Error 0.135 |
Secondary
Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
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 frame: Baseline, Day 1 and Week 12 (Day 85)
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 of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 4h (n=220, 213) | 0.168 liters | Standard Error 0.0132 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -15 min (n=216, 208) | 0.090 liters | Standard Error 0.016 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 1h (n=222, 216) | 0.176 liters | Standard Error 0.0108 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 5 min (n=221, 214) | 0.118 liters | Standard Error 0.0161 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 6h (n=221, 214) | 0.132 liters | Standard Error 0.0135 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 15 min (n=222, 216) | 0.171 liters | Standard Error 0.0164 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 15 min (n=222, 216) | 0.129 liters | Standard Error 0.0085 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 1h (n=222, 216) | 0.178 liters | Standard Error 0.0166 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 8h (n=220, 214) | 0.113 liters | Standard Error 0.0129 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 2h (n=221, 216) | 0.186 liters | Standard Error 0.0178 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 2h (n=221, 216) | 0.198 liters | Standard Error 0.012 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 11h 55min (n=216, 207) | 0.083 liters | Standard Error 0.0131 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 6h (n=221, 214) | 0.120 liters | Standard Error 0.0183 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 5 min (n=221, 214) | 0.074 liters | Standard Error 0.0075 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 8h (n=220, 214) | 0.080 liters | Standard Error 0.018 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -45 min (n=217, 208) | 0.092 liters | Standard Error 0.0154 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 11h 55min (n=216, 207) | 0.072 liters | Standard Error 0.0165 |
| NVA237 | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 4h (n=220, 213) | 0.147 liters | Standard Error 0.018 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 11h 55min (n=216, 207) | -0.043 liters | Standard Error 0.0165 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 5 min (n=221, 214) | 0.015 liters | Standard Error 0.0074 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 15 min (n=222, 216) | 0.015 liters | Standard Error 0.0084 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 1h (n=222, 216) | 0.008 liters | Standard Error 0.0106 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 2h (n=221, 216) | 0.031 liters | Standard Error 0.0118 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 4h (n=220, 213) | 0.028 liters | Standard Error 0.0129 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 6h (n=221, 214) | 0.000 liters | Standard Error 0.0134 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 8h (n=220, 214) | -0.022 liters | Standard Error 0.0128 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 11h 55min (n=216, 207) | -0.046 liters | Standard Error 0.0131 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -45 min (n=217, 208) | -0.040 liters | Standard Error 0.0158 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -15 min (n=216, 208) | -0.022 liters | Standard Error 0.0162 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 5 min (n=221, 214) | -0.018 liters | Standard Error 0.0163 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 15 min (n=222, 216) | -0.016 liters | Standard Error 0.0168 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 1h (n=222, 216) | -0.014 liters | Standard Error 0.0169 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 2h (n=221, 216) | 0.006 liters | Standard Error 0.0183 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 4h (n=220, 213) | 0.014 liters | Standard Error 0.0182 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 6h (n=221, 214) | -0.026 liters | Standard Error 0.0183 |
| Placebo | Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 8h (n=220, 214) | -0.036 liters | Standard Error 0.0181 |
Secondary
Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.
Time frame: Baseline, Day 1 and Week 12 (Day 85)
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 of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 5 min (n=221, 214) | 0.175 liters | Standard Error 0.0152 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 15 min (n=222, 216) | 0.265 liters | Standard Error 0.0181 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 1h (n=222, 216) | 0.318 liters | Standard Error 0.0207 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 2h (n=221, 216) | 0.351 liters | Standard Error 0.0216 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 4h (n=220, 213) | 0.290 liters | Standard Error 0.0235 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 6h (n=221, 214) | 0.252 liters | Standard Error 0.0235 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 8h (n=220, 214) | 0.192 liters | Standard Error 0.0221 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 11h 55min (n=216, 207) | 0.152 liters | Standard Error 0.0234 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -45 min (n=217, 208) | 0.162 liters | Standard Error 0.0289 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -15 min (n=216, 208) | 0.156 liters | Standard Error 0.0283 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 5 min (n=221, 214) | 0.184 liters | Standard Error 0.0282 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 15 min (n=222, 216) | 0.263 liters | Standard Error 0.0288 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 1h (n=222, 216) | 0.258 liters | Standard Error 0.0297 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 2h (n=221, 216) | 0.277 liters | Standard Error 0.0299 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 4h (n=220, 213) | 0.215 liters | Standard Error 0.0317 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 6h (n=221, 214) | 0.199 liters | Standard Error 0.0304 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 8h (n=220, 214) | 0.128 liters | Standard Error 0.0303 |
| NVA237 | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 11h 55min (n=216, 207) | 0.110 liters | Standard Error 0.0286 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 2h (n=221, 216) | 0.033 liters | Standard Error 0.0307 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 5 min (n=221, 214) | 0.037 liters | Standard Error 0.0152 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -15 min (n=216, 208) | -0.017 liters | Standard Error 0.0287 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 15 min (n=222, 216) | 0.044 liters | Standard Error 0.018 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 11h 55min (n=216, 207) | -0.006 liters | Standard Error 0.0288 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 1h (n=222, 216) | 0.032 liters | Standard Error 0.0205 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 5 min (n=221, 214) | -0.007 liters | Standard Error 0.0287 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 2h (n=221, 216) | 0.071 liters | Standard Error 0.0213 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 4h (n=220, 213) | 0.076 liters | Standard Error 0.0321 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 4h (n=220, 213) | 0.067 liters | Standard Error 0.0231 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 15 min (n=222, 216) | -0.003 liters | Standard Error 0.0294 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 6h (n=221, 214) | 0.022 liters | Standard Error 0.0234 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 8h (n=220, 214) | -0.023 liters | Standard Error 0.0305 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 8h (n=220, 214) | -0.009 liters | Standard Error 0.022 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 1h (n=222, 216) | 0.004 liters | Standard Error 0.0302 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 1/ 11h 55min (n=216, 207) | -0.030 liters | Standard Error 0.0235 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ 6h (n=221, 214) | -0.015 liters | Standard Error 0.0305 |
| Placebo | Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85) | DAY 85/ -45 min (n=217, 208) | -0.043 liters | Standard Error 0.0296 |
Secondary
Change From Baseline of Morning and Nighttime Symptom Scores at Week 12
Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am & each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least & 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day & night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day & night scores.
Time frame: 12 weeks
Population: Participants from the full analysis set (FAS), who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed only and included all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| NVA237 | Change From Baseline of Morning and Nighttime Symptom Scores at Week 12 | Daytime total symptom score (n=208,202) | -1.14 score | Standard Error 0.133 |
| NVA237 | Change From Baseline of Morning and Nighttime Symptom Scores at Week 12 | nighttime total symptom score (n=207,202) | -1.22 score | Standard Error 0.143 |
| Placebo | Change From Baseline of Morning and Nighttime Symptom Scores at Week 12 | Daytime total symptom score (n=208,202) | -0.73 score | Standard Error 0.13 |
| Placebo | Change From Baseline of Morning and Nighttime Symptom Scores at Week 12 | nighttime total symptom score (n=207,202) | -0.95 score | Standard Error 0.139 |
Secondary
Percentage of Days Able to Perform Usual Daily Activities
Patients are reporting symptoms by using an electronic diary. 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.
Time frame: from Baseline up to 12 weeks
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 | Percentage of Days Able to Perform Usual Daily Activities | 8.6 pecentage of days | Standard Error 2.2 |
| Placebo | Percentage of Days Able to Perform Usual Daily Activities | 1.8 pecentage of days | Standard Error 2.15 |
Secondary
Percentage of Days With no Daytime Symptoms
Patients are reporting symptoms by using an electronic diary. 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. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100.
Time frame: from Baseline up to 12 weeks
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 | Percentage of Days With no Daytime Symptoms | 5.1 percentage of days | Standard Error 1.65 |
| Placebo | Percentage of Days With no Daytime Symptoms | 2.5 percentage of days | Standard Error 1.62 |
Secondary
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 percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization.
Time frame: 12 weeks
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 | Percentage of Days Without Rescue Medication Use | 16.6 percentage of days | Standard Error 2.37 |
| Placebo | Percentage of Days Without Rescue Medication Use | 10.5 percentage of days | Standard Error 2.31 |
Secondary
Percentage of Nights With no Nighttime Awakenings
Patients are reporting symptoms by using an electronic diary. A night with no nighttime awakening is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks.
Time frame: from Baseline up to 12 weeks
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 | Percentage of Nights With no Nighttime Awakenings | 13.3 percentage of nights | Standard Error 2 |
| Placebo | Percentage of Nights With no Nighttime Awakenings | 11.3 percentage of nights | Standard Error 1.97 |
Secondary
Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at Week 12
The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). 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 significant improvement in SGRQ is defined as less than or equal to -4 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVA237 | Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at Week 12 | 49.0 percentage of participants |
| Placebo | Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at Week 12 | 40.6 percentage of participants |
Secondary
The Average 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 mean daily number of puffs used per patient over the 12 weeks treatment period.
Time frame: baseline and 12 weeks
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 | The Average Number of Puffs of Rescue Medication Per Day | -1.63 number of puffs | Standard Error 0.18 |
| Placebo | The Average Number of Puffs of Rescue Medication Per Day | -0.86 number of puffs | Standard Error 0.177 |