Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
QVA149, COPD, combination bronchodilator, indacaterol, glycopyrronium bromide
Brief summary
The purpose of this study is to provide pivotal efficacy and safety data for QVA149 in patients with moderate to severe COPD.
Interventions
Capsules for inhalation delivered via SDDPI.
DRUGglycopyrronium (NVA237)
Capsules for inhalation delivered via SDDPI.
Capsules for inhalation delivered via SDDPI.
DRUGtiotropium
Capsules for inhalation delivered via HandiHaler® device.
DRUGplacebo
Placebo to match capsules for inhalation delivered via SDDPI.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults aged ≥40 yrs * Smoking history of at least 10 pack years * Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008) * Post-bronchodilator FEV1 \< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) \<70%
Exclusion criteria
* Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1 * Patients with concomitant pulmonary disease * Patients with a history of asthma * Any patient with lung cancer or a history of lung cancer * Patients with a history of certain cardiovascular co-morbid conditions * Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency * Patients in the active phase of a supervised pulmonary rehabilitation program * Patients contraindicated for inhaled anticholinergic agents and β2 agonists * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment | 23 hours 15 minutes and 23 hour 45 minute post-dose Week 26 | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 26 | 26 weeks | SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. A mixed model was used with treatment as a fixed effect with Baseline SGRQ and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Over 26 Weeks | Baseline, Week 26 | The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient. Rescue medication data recorded during the 14 day run-in was used to calculate the baseline. A negative change from baseline indicates improvement. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo | 23 hours 15 minutes and 23 hour 45 minute post-dose Week 26 | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149 Compared to Tiotropium | 23 hours 15 minutes and 23 hour 45 minute post-dose Week 26 | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | Baseline, Week 12, Week 26 | A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. 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. A mixed model was used with treatment as a fixed effect with Baseline Dyspnea Index Score and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators as covariates and included baseline smoking status, baseline inhaled corticosteroids and region as fixed effects with center nested within region as a random effect. |
| Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment | Baseline, Week 26 | A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing) at Week 12 and Week 26. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. The BDI (baseline) was measured at Day 1. The TDI captures changes from baseline. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. |
| St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | Week 12, Week 26 | SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. A mixed model was used with treatment as a fixed effect with Baseline SGRQ and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment | Baseline, Week 26 | SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. |
| Percentage of Nights With No Night Time Awakenings Over 26 Weeks | 26 Weeks | A day with no night time awakenings is defined from the diary data as any day where the patient did not wake up due to COPD symptoms. The percentage of nights is calculated by the number of days with no nighttime awakenings/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Percentage of Days With No Daytime Symptoms Over 26 Weeks | 26 Weeks | A day with no day time symptoms is defined from the diary data as any day where the patient recorded no coughing, no wheezing, no sputum production and no breathlessness during the previous 12 hours (approximately 8AM to 8PM). The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent of days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Transitional Dyspnea Index (TDI) Focal Score at Week 26 | Week 26 | A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). 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. A mixed model was used with treatment as a fixed effect with Baseline Dyspnea Index Score and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Baseline, Week 12, Week 26 | The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient. Rescue medication data recorded during the 14 day run-in was used to calculate the baseline. A negative change from baseline indicates improvement. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Baseline, Week 26 | The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs in the morning and evening were calculated and divided by the number of days with data to determine the mean daily number of daytime and nighttime puffs. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline (BL) ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Percentage of Days With no Rescue Medication Use Over 26 Weeks | 26 Weeks | A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. The percentage of days is calculated by the number of days with no rescue medicine use/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | From 5 minutes to 4 hours post-dose Day 1 and Week 26 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | From 5 minutes to 12 hours post-dose Day 1 and Week 26 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 8, 12 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26 | From 5 minutes to 23 hours 45 minutes post-dose Week 26 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 8, 12, 23 hours 15 minutes and 23 hours 45 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
| 24 Hour Holter Monitoring in a Subset of Patients | Week 12, Week 26 | 24-hourly mean heart rate was performed using a Holter Monitor at Weeks 12 and 26 in a subgroup of patients. Mixed model: heart rate = treatment + baseline heart rate + baseline smoking status + baseline ICS use + region + center (region) + error. Center was included as a random effect nested within region. The 24-hourly mean heart rate is the mean heart rate over the 24 hour period, derived using hourly mean heart rate beats per minute. |
| Rate of Moderate or Severe COPD Exacerbation | 26 Weeks | Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years |
| Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period | 26 Weeks | — |
| Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | 26 Weeks | — |
| Percentage of Days Able to Perform Usual Daily Activities Over 26 Weeks | 26 Weeks | Patients answered the question Did your respiratory symptoms stop you performing your usual activities today?-Not at all in their daily diary. The percentage of days is calculated by the number of days patient is able to perform daily activities/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent of Days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect. |
Countries
Australia, Bulgaria, Canada, France, Germany, Guatemala, Hungary, Japan, Philippines, Poland, Russia, Slovakia, South Africa, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
There was a 14 day run-in period prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol and Glycopyrronium (QVA149) QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study. | 474 |
| Indacaterol (QAB149) QAB149 150 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study. | 476 |
| Glycopyrronium (NVA237) NVA237 50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study. | 473 |
| Tiotropium Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study. | 480 |
| Placebo Matching Placebo capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study. | 232 |
| Total | 2,135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Abnormal test procedure result (s) | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Administrative problems | 3 | 2 | 1 | 1 | 2 |
| Overall Study | Adverse Event | 5 | 23 | 13 | 10 | 10 |
| Overall Study | Death | 1 | 1 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 4 | 1 |
| Overall Study | Protocol deviation | 14 | 8 | 12 | 10 | 11 |
| Overall Study | Subject withdrew consent | 12 | 13 | 22 | 11 | 13 |
| Overall Study | Unsatisfactory therapeutic effect | 2 | 8 | 2 | 5 | 8 |
Baseline characteristics
| Characteristic | Indacaterol and Glycopyrronium (QVA149) | Indacaterol (QAB149) | Glycopyrronium (NVA237) | Tiotropium | Placebo | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 64.0 years STANDARD_DEVIATION 8.88 | 63.6 years STANDARD_DEVIATION 8.78 | 64.3 years STANDARD_DEVIATION 9.04 | 63.5 years STANDARD_DEVIATION 8.73 | 64.4 years STANDARD_DEVIATION 8.58 | 63.9 years STANDARD_DEVIATION 8.83 |
| Sex: Female, Male Female | 112 Participants | 122 Participants | 108 Participants | 120 Participants | 63 Participants | 525 Participants |
| Sex: Female, Male Male | 362 Participants | 354 Participants | 365 Participants | 360 Participants | 169 Participants | 1610 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 166 / 474 | 189 / 476 | 185 / 473 | 172 / 480 | 102 / 232 |
| serious Total, serious adverse events | 22 / 474 | 26 / 476 | 29 / 473 | 19 / 480 | 13 / 232 |
Outcome results
Primary
Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 23 hours 15 minutes and 23 hour 45 minute post-dose Week 26
Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis. Data was imputed with last observation carried forward. Data within 6 hours of rescue medication use or 7 days of systemic corticosteroid use is excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment | 1.45 Liters | Standard Error 0.01 |
| Indacaterol (QAB149) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment | 1.38 Liters | Standard Error 0.01 |
| Glycopyrronium (NVA237) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment | 1.36 Liters | Standard Error 0.01 |
Secondary
24 Hour Holter Monitoring in a Subset of Patients
24-hourly mean heart rate was performed using a Holter Monitor at Weeks 12 and 26 in a subgroup of patients. Mixed model: heart rate = treatment + baseline heart rate + baseline smoking status + baseline ICS use + region + center (region) + error. Center was included as a random effect nested within region. The 24-hourly mean heart rate is the mean heart rate over the 24 hour period, derived using hourly mean heart rate beats per minute.
Time frame: Week 12, Week 26
Population: Safety Set Holter Group-a subset of the Safety participants that included all randomized participants who received at least one dose of study drug and participated in the 24 hour Holter monitoring with evaluable data available for analysis. No participants in the Titotropium arm participated in the Holter Monitoring.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | 24 Hour Holter Monitoring in a Subset of Patients | Week 12 (n=35,38,27,15) | 80.8 beats per minute | Standard Error 1.5 |
| Indacaterol and Glycopyrronium (QVA149) | 24 Hour Holter Monitoring in a Subset of Patients | Week 26 (n=36,36,26,16) | 79.8 beats per minute | Standard Error 1.68 |
| Indacaterol (QAB149) | 24 Hour Holter Monitoring in a Subset of Patients | Week 26 (n=36,36,26,16) | 78.6 beats per minute | Standard Error 1.57 |
| Indacaterol (QAB149) | 24 Hour Holter Monitoring in a Subset of Patients | Week 12 (n=35,38,27,15) | 79.9 beats per minute | Standard Error 1.35 |
| Glycopyrronium (NVA237) | 24 Hour Holter Monitoring in a Subset of Patients | Week 12 (n=35,38,27,15) | 79.4 beats per minute | Standard Error 1.57 |
| Glycopyrronium (NVA237) | 24 Hour Holter Monitoring in a Subset of Patients | Week 26 (n=36,36,26,16) | 80.5 beats per minute | Standard Error 1.75 |
| Placebo | 24 Hour Holter Monitoring in a Subset of Patients | Week 12 (n=35,38,27,15) | 78.9 beats per minute | Standard Error 1.95 |
| Placebo | 24 Hour Holter Monitoring in a Subset of Patients | Week 26 (n=36,36,26,16) | 77.0 beats per minute | Standard Error 2.09 |
Secondary
Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26
A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. 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. A mixed model was used with treatment as a fixed effect with Baseline Dyspnea Index Score and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators as covariates and included baseline smoking status, baseline inhaled corticosteroids and region as fixed effects with center nested within region as a random effect.
Time frame: Baseline, Week 12, Week 26
Population: Participants from the Full Analysis Set, included all participants who received at least one dose of study drug, with data available for analysis. Missing data were imputed with Last Observation Carried Forward but not more than 14 weeks and data within 4 weeks of day 1 were not carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_ baseline for Week 12 | 6.45 Score on a scale | Standard Error 0.1 |
| Indacaterol and Glycopyrronium (QVA149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 12 | 2.44 Score on a scale | Standard Error 0.158 |
| Indacaterol and Glycopyrronium (QVA149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_baseline for Week 26 (n=439,440,424,441,193) | 6.45 Score on a scale | Standard Error 0.101 |
| Indacaterol and Glycopyrronium (QVA149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 26 (n=439,440,424,441,193) | 2.72 Score on a scale | Standard Error 0.17 |
| Indacaterol (QAB149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_ baseline for Week 12 | 6.28 Score on a scale | Standard Error 0.096 |
| Indacaterol (QAB149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 26 (n=439,440,424,441,193) | 2.47 Score on a scale | Standard Error 0.171 |
| Indacaterol (QAB149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 12 | 2.18 Score on a scale | Standard Error 0.157 |
| Indacaterol (QAB149) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_baseline for Week 26 (n=439,440,424,441,193) | 6.28 Score on a scale | Standard Error 0.097 |
| Glycopyrronium (NVA237) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 26 (n=439,440,424,441,193) | 2.52 Score on a scale | Standard Error 0.172 |
| Glycopyrronium (NVA237) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 12 | 2.04 Score on a scale | Standard Error 0.158 |
| Glycopyrronium (NVA237) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_baseline for Week 26 (n=439,440,424,441,193) | 6.22 Score on a scale | Standard Error 0.097 |
| Glycopyrronium (NVA237) | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_ baseline for Week 12 | 6.21 Score on a scale | Standard Error 0.097 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_ baseline for Week 12 | 6.43 Score on a scale | Standard Error 0.094 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 12 | 1.81 Score on a scale | Standard Error 0.158 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 26 (n=439,440,424,441,193) | 2.21 Score on a scale | Standard Error 0.171 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_baseline for Week 26 (n=439,440,424,441,193) | 6.46 Score on a scale | Standard Error 0.095 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 26 (n=439,440,424,441,193) | 1.63 Score on a scale | Standard Error 0.23 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_baseline for Week 26 (n=439,440,424,441,193) | 6.56 Score on a scale | Standard Error 0.157 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | TDI Week 12 | 1.22 Score on a scale | Standard Error 0.215 |
| Placebo | Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26 | BDI_ baseline for Week 12 | 6.53 Score on a scale | Standard Error 0.154 |
Secondary
Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks
The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs in the morning and evening were calculated and divided by the number of days with data to determine the mean daily number of daytime and nighttime puffs. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline (BL) ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: Baseline, Week 26
Population: Participants from the full analysis, consisting of all randomized participant who received study drug, with data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Nighttime Change from BL (n=418,413,399,422,198) | -0.78 Puffs | Standard Error 0.049 |
| Indacaterol and Glycopyrronium (QVA149) | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Daytime Change from BL (n=415,410,395,418,195) | -1.11 Puffs | Standard Error 0.061 |
| Indacaterol (QAB149) | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Daytime Change from BL (n=415,410,395,418,195) | -0.96 Puffs | Standard Error 0.062 |
| Indacaterol (QAB149) | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Nighttime Change from BL (n=418,413,399,422,198) | -0.63 Puffs | Standard Error 0.049 |
| Glycopyrronium (NVA237) | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Nighttime Change from BL (n=418,413,399,422,198) | -0.48 Puffs | Standard Error 0.05 |
| Glycopyrronium (NVA237) | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Daytime Change from BL (n=415,410,395,418,195) | -0.75 Puffs | Standard Error 0.063 |
| Placebo | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Daytime Change from BL (n=415,410,395,418,195) | -0.83 Puffs | Standard Error 0.061 |
| Placebo | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Nighttime Change from BL (n=418,413,399,422,198) | -0.52 Puffs | Standard Error 0.049 |
| Placebo | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Daytime Change from BL (n=415,410,395,418,195) | -0.58 Puffs | Standard Error 0.086 |
| Placebo | Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks | Nighttime Change from BL (n=418,413,399,422,198) | -0.34 Puffs | Standard Error 0.069 |
Secondary
Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26
The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient. Rescue medication data recorded during the 14 day run-in was used to calculate the baseline. A negative change from baseline indicates improvement. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: Baseline, Week 12, Week 26
Population: Participants from the full analysis, consisting of all randomized participant who received study drug, with data available for analysis at Week 12 and Week 26.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from Baseline (BL) at Week 12 | -1.82 Puffs per day | Standard Error 0.102 |
| Indacaterol and Glycopyrronium (QVA149) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from BL at Week 26 (n=419,416,403,424,199) | -1.88 Puffs per day | Standard Error 0.105 |
| Indacaterol (QAB149) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from Baseline (BL) at Week 12 | -1.46 Puffs per day | Standard Error 0.102 |
| Indacaterol (QAB149) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from BL at Week 26 (n=419,416,403,424,199) | -1.57 Puffs per day | Standard Error 0.106 |
| Glycopyrronium (NVA237) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from Baseline (BL) at Week 12 | -1.22 Puffs per day | Standard Error 0.103 |
| Glycopyrronium (NVA237) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from BL at Week 26 (n=419,416,403,424,199) | -1.22 Puffs per day | Standard Error 0.107 |
| Placebo | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from BL at Week 26 (n=419,416,403,424,199) | -1.34 Puffs per day | Standard Error 0.105 |
| Placebo | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from Baseline (BL) at Week 12 | -1.28 Puffs per day | Standard Error 0.102 |
| Placebo | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from Baseline (BL) at Week 12 | -0.83 Puffs per day | Standard Error 0.141 |
| Placebo | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26 | Change from BL at Week 26 (n=419,416,403,424,199) | -0.92 Puffs per day | Standard Error 0.147 |
Secondary
Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Over 26 Weeks
The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient. Rescue medication data recorded during the 14 day run-in was used to calculate the baseline. A negative change from baseline indicates improvement. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: Baseline, Week 26
Population: Participants from the full analysis, consisting of all randomized participant who received study drug, with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Over 26 Weeks | -1.88 Puffs per day | Standard Error 0.105 |
| Indacaterol (QAB149) | Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Over 26 Weeks | -0.92 Puffs per day | Standard Error 0.147 |
Secondary
Percentage of Days Able to Perform Usual Daily Activities Over 26 Weeks
Patients answered the question Did your respiratory symptoms stop you performing your usual activities today?-Not at all in their daily diary. The percentage of days is calculated by the number of days patient is able to perform daily activities/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent of Days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 26 Weeks
Population: Participants from the Full Analysis Set, all randomized participants who received study drug, with evaluable diary data (at least 40 days) for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Days Able to Perform Usual Daily Activities Over 26 Weeks | 45.97 Percentage of days | Standard Error 1.578 |
| Indacaterol (QAB149) | Percentage of Days Able to Perform Usual Daily Activities Over 26 Weeks | 40.94 Percentage of days | Standard Error 1.582 |
| Glycopyrronium (NVA237) | Percentage of Days Able to Perform Usual Daily Activities Over 26 Weeks | 40.10 Percentage of days | Standard Error 1.607 |
| Placebo | Percentage of Days Able to Perform Usual Daily Activities Over 26 Weeks | 37.52 Percentage of days | Standard Error 1.572 |
| Placebo | Percentage of Days Able to Perform Usual Daily Activities Over 26 Weeks | 34.49 Percentage of days | Standard Error 2.197 |
Secondary
Percentage of Days With No Daytime Symptoms Over 26 Weeks
A day with no day time symptoms is defined from the diary data as any day where the patient recorded no coughing, no wheezing, no sputum production and no breathlessness during the previous 12 hours (approximately 8AM to 8PM). The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent of days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 26 Weeks
Population: Participants from the Full Analysis Set, all randomized participants who received study drug, with evaluable diary data (at least 40 days) for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Days With No Daytime Symptoms Over 26 Weeks | 7.49 Percentage of days | Standard Error 0.931 |
| Indacaterol (QAB149) | Percentage of Days With No Daytime Symptoms Over 26 Weeks | 9.17 Percentage of days | Standard Error 0.933 |
| Glycopyrronium (NVA237) | Percentage of Days With No Daytime Symptoms Over 26 Weeks | 6.40 Percentage of days | Standard Error 0.948 |
| Placebo | Percentage of Days With No Daytime Symptoms Over 26 Weeks | 5.54 Percentage of days | Standard Error 0.928 |
| Placebo | Percentage of Days With No Daytime Symptoms Over 26 Weeks | 4.44 Percentage of days | Standard Error 1.294 |
Secondary
Percentage of Days With no Rescue Medication Use Over 26 Weeks
A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. The percentage of days is calculated by the number of days with no rescue medicine use/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 26 Weeks
Population: Participants from the full analysis set (all randomized participants who received at least one dose of study drug) with evaluable data (at least 40 days of diary data) available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Days With no Rescue Medication Use Over 26 Weeks | 47.09 Percentage of days | Standard Error 1.752 |
| Indacaterol (QAB149) | Percentage of Days With no Rescue Medication Use Over 26 Weeks | 44.81 Percentage of days | Standard Error 1.764 |
| Glycopyrronium (NVA237) | Percentage of Days With no Rescue Medication Use Over 26 Weeks | 37.74 Percentage of days | Standard Error 1.79 |
| Placebo | Percentage of Days With no Rescue Medication Use Over 26 Weeks | 36.51 Percentage of days | Standard Error 1.752 |
| Placebo | Percentage of Days With no Rescue Medication Use Over 26 Weeks | 34.76 Percentage of days | Standard Error 2.437 |
Secondary
Percentage of Nights With No Night Time Awakenings Over 26 Weeks
A day with no night time awakenings is defined from the diary data as any day where the patient did not wake up due to COPD symptoms. The percentage of nights is calculated by the number of days with no nighttime awakenings/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 26 Weeks
Population: Participants from the Full Analysis Set, all randomized participants who received study drug, with evaluable diary data (at least 40 days) for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Nights With No Night Time Awakenings Over 26 Weeks | 63.68 Percentage of nights | Standard Error 1.473 |
| Indacaterol (QAB149) | Percentage of Nights With No Night Time Awakenings Over 26 Weeks | 62.48 Percentage of nights | Standard Error 1.479 |
| Glycopyrronium (NVA237) | Percentage of Nights With No Night Time Awakenings Over 26 Weeks | 58.64 Percentage of nights | Standard Error 1.5 |
| Placebo | Percentage of Nights With No Night Time Awakenings Over 26 Weeks | 60.00 Percentage of nights | Standard Error 1.469 |
| Placebo | Percentage of Nights With No Night Time Awakenings Over 26 Weeks | 53.67 Percentage of nights | Standard Error 2.047 |
Secondary
Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization
Time frame: 26 Weeks
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Corticosteroids_Antibiotics-No hospitalization | 16.7 Percentage of participants |
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Requiring hospitalization | 2.1 Percentage of participants |
| Indacaterol (QAB149) | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Requiring hospitalization | 2.5 Percentage of participants |
| Indacaterol (QAB149) | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Corticosteroids_Antibiotics-No hospitalization | 19.7 Percentage of participants |
| Glycopyrronium (NVA237) | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Corticosteroids_Antibiotics-No hospitalization | 17.8 Percentage of participants |
| Glycopyrronium (NVA237) | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Requiring hospitalization | 1.9 Percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Requiring hospitalization | 1.0 Percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Corticosteroids_Antibiotics-No hospitalization | 16.9 Percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Corticosteroids_Antibiotics-No hospitalization | 23.3 Percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization | Requiring hospitalization | 3.0 Percentage of participants |
Secondary
Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment
SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status.
Time frame: Baseline, Week 26
Population: Participants from the Full Analysis Set, that included all participants who received at least one dose of study drug, with data available for analysis. Missing data were imputed with Last Observation Carried Forward but not more than 14 weeks and data within 4 weeks of day 1 were not carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment | 63.7 Percentage of participants |
| Indacaterol (QAB149) | Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment | 63.0 Percentage of participants |
| Glycopyrronium (NVA237) | Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment | 60.5 Percentage of participants |
| Placebo | Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment | 56.4 Percentage of participants |
| Placebo | Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment | 56.6 Percentage of participants |
Secondary
Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment
A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing) at Week 12 and Week 26. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. The BDI (baseline) was measured at Day 1. The TDI captures changes from baseline. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9.
Time frame: Baseline, Week 26
Population: Participants from the Full Analysis Set, included all participants who received at least one dose of study drug, with data available for analysis. Missing data were imputed with Last Observation Carried Forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment | 68.1 Percentage of participants |
| Indacaterol (QAB149) | Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment | 64.6 Percentage of participants |
| Glycopyrronium (NVA237) | Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment | 63.7 Percentage of participants |
| Placebo | Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment | 59.2 Percentage of participants |
| Placebo | Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment | 57.5 Percentage of participants |
Secondary
Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period
Time frame: 26 Weeks
Population: Full Analysis Set includes all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period | 17.9 Percentage of participants |
| Indacaterol (QAB149) | Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period | 21.6 Percentage of participants |
| Glycopyrronium (NVA237) | Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period | 18.8 Percentage of participants |
| Placebo | Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period | 17.7 Percentage of participants |
| Placebo | Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period | 25.8 Percentage of participants |
Secondary
Rate of Moderate or Severe COPD Exacerbation
Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
Time frame: 26 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Rate of Moderate or Severe COPD Exacerbation | 0.46 Exacerbations per year |
| Indacaterol (QAB149) | Rate of Moderate or Severe COPD Exacerbation | 0.59 Exacerbations per year |
| Glycopyrronium (NVA237) | Rate of Moderate or Severe COPD Exacerbation | 0.52 Exacerbations per year |
| Placebo | Rate of Moderate or Severe COPD Exacerbation | 0.45 Exacerbations per year |
| Placebo | Rate of Moderate or Severe COPD Exacerbation | 0.75 Exacerbations per year |
Secondary
Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 8, 12 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: From 5 minutes to 12 hours post-dose Day 1 and Week 26
Population: Participants from the 24 hour serial spirometry subset of the full analysis set (all randomized participants who received study drug) with data available for analysis. Data within 6 hours of rescue medication use or 7 days of systemic corticosteroid use is excluded from the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Day1 | 1.50 Liters | Standard Error 0.017 |
| Indacaterol and Glycopyrronium (QVA149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Week 26 (n=60,55,58,67,27) | 1.52 Liters | Standard Error 0.027 |
| Indacaterol (QAB149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Day1 | 1.40 Liters | Standard Error 0.017 |
| Indacaterol (QAB149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Week 26 (n=60,55,58,67,27) | 1.39 Liters | Standard Error 0.027 |
| Glycopyrronium (NVA237) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Day1 | 1.42 Liters | Standard Error 0.018 |
| Glycopyrronium (NVA237) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Week 26 (n=60,55,58,67,27) | 1.39 Liters | Standard Error 0.028 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Week 26 (n=60,55,58,67,27) | 1.39 Liters | Standard Error 0.027 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Day1 | 1.38 Liters | Standard Error 0.017 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Day1 | 1.24 Liters | Standard Error 0.023 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26 | Week 26 (n=60,55,58,67,27) | 1.18 Liters | Standard Error 0.036 |
Secondary
Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 8, 12, 23 hours 15 minutes and 23 hours 45 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: From 5 minutes to 23 hours 45 minutes post-dose Week 26
Population: Participants from the 24 hour serial spirometry subset of the full analysis set (all randomized participants who received study drug) with data available for analysis. Data within 6 hours of rescue medication use or 7 days of systemic corticosteroid use is excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26 | 1.46 Liters | Standard Error 0.026 |
| Indacaterol (QAB149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26 | 1.35 Liters | Standard Error 0.027 |
| Glycopyrronium (NVA237) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26 | 1.35 Liters | Standard Error 0.027 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26 | 1.36 Liters | Standard Error 0.026 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26 | 1.15 Liters | Standard Error 0.036 |
Secondary
Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: From 5 minutes to 4 hours post-dose Day 1 and Week 26
Population: Participants from full analysis set, all randomized participants who received study drug, with data available for analysis. Data within 6 hours of rescue medication use or 7 days of systemic corticosteroid use is excluded from analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Day 1 | 1.52 Liters | Standard Error 0.006 |
| Indacaterol and Glycopyrronium (QVA149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Week 26 (n=433,418,412,435,186) | 1.57 Liters | Standard Error 0.01 |
| Indacaterol (QAB149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Day 1 | 1.46 Liters | Standard Error 0.006 |
| Indacaterol (QAB149) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Week 26 (n=433,418,412,435,186) | 1.46 Liters | Standard Error 0.01 |
| Glycopyrronium (NVA237) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Day 1 | 1.49 Liters | Standard Error 0.006 |
| Glycopyrronium (NVA237) | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Week 26 (n=433,418,412,435,186) | 1.43 Liters | Standard Error 0.01 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Week 26 (n=433,418,412,435,186) | 1.44 Liters | Standard Error 0.01 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Day 1 | 1.44 Liters | Standard Error 0.006 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Day 1 | 1.30 Liters | Standard Error 0.008 |
| Placebo | Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26 | Week 26 (n=433,418,412,435,186) | 1.23 Liters | Standard Error 0.015 |
Secondary
St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment
SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. A mixed model was used with treatment as a fixed effect with Baseline SGRQ and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: Week 12, Week 26
Population: Participants from the Full Analysis Set, included all participants who received at least one dose of study drug, with data available for analysis. Missing data were imputed with Last Observation Carried Forward but not more than 14 weeks and data within 4 weeks of day 1 were not carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 12 Weeks | 37.56 Score on a scale | Standard Error 0.659 |
| Indacaterol and Glycopyrronium (QVA149) | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 26 Weeks (n=441,443,430,450,196) | 37.01 Score on a scale | Standard Error 0.679 |
| Indacaterol (QAB149) | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 12 Weeks | 38.55 Score on a scale | Standard Error 0.662 |
| Indacaterol (QAB149) | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 26 Weeks (n=441,443,430,450,196) | 38.10 Score on a scale | Standard Error 0.68 |
| Glycopyrronium (NVA237) | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 12 Weeks | 39.40 Score on a scale | Standard Error 0.663 |
| Glycopyrronium (NVA237) | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 26 Weeks (n=441,443,430,450,196) | 38.19 Score on a scale | Standard Error 0.686 |
| Placebo | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 26 Weeks (n=441,443,430,450,196) | 39.14 Score on a scale | Standard Error 0.677 |
| Placebo | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 12 Weeks | 39.94 Score on a scale | Standard Error 0.658 |
| Placebo | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 12 Weeks | 41.55 Score on a scale | Standard Error 0.9 |
| Placebo | St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment | 26 Weeks (n=441,443,430,450,196) | 40.02 Score on a scale | Standard Error 0.941 |
Secondary
St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 26
SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. A mixed model was used with treatment as a fixed effect with Baseline SGRQ and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 26 weeks
Population: Participants from the Full Analysis Set,included all participants who received at least one dose of study drug, with data available for analysis. Missing data were imputed with Last Observation Carried Forward but not more than 14 weeks and data within 4 weeks of day 1 were not carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 26 | 37.01 Score on a scale | Standard Error 0.679 |
| Indacaterol (QAB149) | St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 26 | 40.02 Score on a scale | Standard Error 0.941 |
Secondary
Transitional Dyspnea Index (TDI) Focal Score at Week 26
A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). 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. A mixed model was used with treatment as a fixed effect with Baseline Dyspnea Index Score and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: Week 26
Population: Participants from the Full Analysis Set, included all participants who received at least one dose of study drug, with data available for analysis. Missing data were imputed with Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Transitional Dyspnea Index (TDI) Focal Score at Week 26 | 2.72 Score on a scale | Standard Error 0.17 |
| Indacaterol (QAB149) | Transitional Dyspnea Index (TDI) Focal Score at Week 26 | 1.63 Score on a scale | Standard Error 0.23 |
Secondary
Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149 Compared to Tiotropium
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 23 hours 15 minutes and 23 hour 45 minute post-dose Week 26
Population: Participants from the Per-protocol Set, randomized participants who received at least one dose of study drug without major protocol deviations. Data was imputed with last observation carried forward. Data within 6 hours of rescue medication use or 7 days of systemic corticosteroid use is excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149 Compared to Tiotropium | 1.46 Liters | Standard Error 0.011 |
| Indacaterol (QAB149) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149 Compared to Tiotropium | 1.39 Liters | Standard Error 0.011 |
Secondary
Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Time frame: 23 hours 15 minutes and 23 hour 45 minute post-dose Week 26
Population: Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis. Data was imputed with last observation carried forward. Data within 6 hours of rescue medication use or 7 days of systemic corticosteroid use is excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo | 1.45 Liters | Standard Error 0.01 |
| Indacaterol (QAB149) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo | 1.38 Liters | Standard Error 0.01 |
| Glycopyrronium (NVA237) | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo | 1.36 Liters | Standard Error 0.01 |
| Placebo | Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo | 1.25 Liters | Standard Error 0.015 |