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A Study to Assess the Efficacy, Safety and Tolerability of Once-daily (q.d.) QVA149 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (SHINE)

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ClinicalTrials.gov Identifier: NCT01202188
Recruitment Status : Completed
First Posted : September 15, 2010
Results First Posted : May 3, 2013
Last Update Posted : September 9, 2013
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: indacaterol and glycopyrronium (QVA149)
Drug: glycopyrronium (NVA237)
Drug: indacaterol (QAB149)
Drug: tiotropium
Drug: placebo
Enrollment 2144
Recruitment Details  
Pre-assignment Details There was a 14 day run-in period prior to randomization.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description 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. 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. NVA237 50 μg capsules for inhalation delivered once daily via a 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. 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. 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.
Period Title: Overall Study
Started 475 477 475 483 234
Safety Set; Received Study Drug 474 476 473 480 232
Completed 437 421 422 441 189
Not Completed 38 56 53 42 45
Reason Not Completed
Protocol deviation             14             8             12             10             11
Subject withdrew consent             12             13             22             11             13
Adverse Event             5             23             13             10             10
Administrative problems             3             2             1             1             2
Unsatisfactory therapeutic effect             2             8             2             5             8
Lost to Follow-up             1             1             0             4             1
Death             1             1             1             1             0
Abnormal test procedure result (s)             0             0             2             0             0
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo Total
Hide Arm/Group Description 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. 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. 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 474 476 473 480 232 2135
Hide Baseline Analysis Population Description
Baseline measures are based on the Safety Set that includes all participants who received study drug.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 474 participants 476 participants 473 participants 480 participants 232 participants 2135 participants
64.0  (8.88) 63.6  (8.78) 64.3  (9.04) 63.5  (8.73) 64.4  (8.58) 63.9  (8.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 474 participants 476 participants 473 participants 480 participants 232 participants 2135 participants
Female
112
  23.6%
122
  25.6%
108
  22.8%
120
  25.0%
63
  27.2%
525
  24.6%
Male
362
  76.4%
354
  74.4%
365
  77.2%
360
  75.0%
169
  72.8%
1610
  75.4%
1.Primary Outcome
Title Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237)
Hide Arm/Group Description:
QVA149 110/50 μg capsules for inhalation delivered once daily via a single-dose dry powder inhaler (SDPPI) 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.
QAB149 150 μg capsules for inhalation delivered once daily via a 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.
NVA237 50 μg capsules for inhalation delivered once daily via a 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.
Overall Number of Participants Analyzed 442 435 424
Least Squares Mean (Standard Error)
Unit of Measure: Liters
1.45  (0.010) 1.38  (0.010) 1.36  (0.010)
2.Secondary Outcome
Title Transitional Dyspnea Index (TDI) Focal Score at Week 26
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Placebo
Hide Arm/Group Description:
QVA149 110/50 μg capsules for inhalation delivered once daily via a single-dose dry powder inhaler (SDPPI) 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.
Matching Placebo capsules for inhalation delivered once daily via a 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.
Overall Number of Participants Analyzed 439 193
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
2.72  (0.170) 1.63  (0.230)
3.Secondary Outcome
Title St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 26
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Placebo
Hide Arm/Group Description:
QVA149 110/50 μg capsules for inhalation delivered once daily via a single-dose dry powder inhaler (SDPPI) 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.
Matching Placebo capsules for inhalation delivered once daily via a 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.
Overall Number of Participants Analyzed 441 196
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
37.01  (0.679) 40.02  (0.941)
4.Secondary Outcome
Title Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Over 26 Weeks
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis, consisting of all randomized participant who received study drug, with data available for analysis.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Placebo
Hide Arm/Group Description:
QVA149 110/50 μg capsules for inhalation delivered once daily via a single-dose dry powder inhaler (SDPPI) 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.
Matching Placebo capsules for inhalation delivered once daily via a 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.
Overall Number of Participants Analyzed 419 199
Least Squares Mean (Standard Error)
Unit of Measure: Puffs per day
-1.88  (0.105) -0.92  (0.147)
5.Secondary Outcome
Title Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Placebo
Hide Arm/Group Description:
QVA149 110/50 μg capsules for inhalation delivered once daily via a single-dose dry powder inhaler (SDPPI) 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.
QAB149 150 μg capsules for inhalation delivered once daily via a 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.
NVA237 50 μg capsules for inhalation delivered once daily via a 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.
Matching Placebo capsules for inhalation delivered once daily via a 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.
Overall Number of Participants Analyzed 442 435 424 191
Least Squares Mean (Standard Error)
Unit of Measure: Liters
1.45  (0.010) 1.38  (0.010) 1.36  (0.010) 1.25  (0.015)
6.Secondary Outcome
Title Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149 Compared to Tiotropium
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Tiotropium
Hide Arm/Group Description:
QVA149 110/50 μg capsules for inhalation delivered once daily via a single-dose dry powder inhaler (SDPPI) 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.
Tiotropium 18 μg capsules for inhalation delivered once daily via the manufacturer's proprietary 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.
Overall Number of Participants Analyzed 387 382
Least Squares Mean (Standard Error)
Unit of Measure: Liters
1.46  (0.011) 1.39  (0.011)
7.Secondary Outcome
Title Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 442 443 435 445 200
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
BDI_ baseline for Week 12 6.45  (0.100) 6.28  (0.096) 6.21  (0.097) 6.43  (0.094) 6.53  (0.154)
TDI Week 12 2.44  (0.158) 2.18  (0.157) 2.04  (0.158) 1.81  (0.158) 1.22  (0.215)
BDI_baseline for Week 26 (n=439,440,424,441,193) 6.45  (0.101) 6.28  (0.097) 6.22  (0.097) 6.46  (0.095) 6.56  (0.157)
TDI Week 26 (n=439,440,424,441,193) 2.72  (0.170) 2.47  (0.171) 2.52  (0.172) 2.21  (0.171) 1.63  (0.230)
8.Secondary Outcome
Title Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 474 476 473 480 232
Measure Type: Number
Unit of Measure: Percentage of participants
68.1 64.6 63.7 59.2 57.5
9.Secondary Outcome
Title St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 448 446 441 454 205
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
12 Weeks 37.56  (0.659) 38.55  (0.662) 39.40  (0.663) 39.94  (0.658) 41.55  (0.900)
26 Weeks (n=441,443,430,450,196) 37.01  (0.679) 38.10  (0.680) 38.19  (0.686) 39.14  (0.677) 40.02  (0.941)
10.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 474 476 473 480 232
Measure Type: Number
Unit of Measure: Percentage of participants
63.7 63.0 60.5 56.4 56.6
11.Secondary Outcome
Title Percentage of Nights With "No Night Time Awakenings" Over 26 Weeks
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received study drug, with evaluable diary data (at least 40 days) for analysis.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 418 413 399 422 198
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of nights
63.68  (1.473) 62.48  (1.479) 58.64  (1.500) 60.00  (1.469) 53.67  (2.047)
12.Secondary Outcome
Title Percentage of Days With "No Daytime Symptoms" Over 26 Weeks
Hide Description 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
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Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received study drug, with evaluable diary data (at least 40 days) for analysis.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 415 410 395 418 195
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of days
7.49  (0.931) 9.17  (0.933) 6.40  (0.948) 5.54  (0.928) 4.44  (1.294)
13.Secondary Outcome
Title Percentage of "Days Able to Perform Usual Daily Activities" Over 26 Weeks
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received study drug, with evaluable diary data (at least 40 days) for analysis.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 415 410 395 418 195
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of days
45.97  (1.578) 40.94  (1.582) 40.10  (1.607) 37.52  (1.572) 34.49  (2.197)
14.Secondary Outcome
Title Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 420 420 413 427 203
Least Squares Mean (Standard Error)
Unit of Measure: Puffs per day
Change from Baseline (BL) at Week 12 -1.82  (0.102) -1.46  (0.102) -1.22  (0.103) -1.28  (0.102) -0.83  (0.141)
Change from BL at Week 26 (n=419,416,403,424,199) -1.88  (0.105) -1.57  (0.106) -1.22  (0.107) -1.34  (0.105) -0.92  (0.147)
15.Secondary Outcome
Title Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis, consisting of all randomized participant who received study drug, with data available for analysis.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 474 476 473 480 232
Least Squares Mean (Standard Error)
Unit of Measure: Puffs
Daytime Change from BL (n=415,410,395,418,195) -1.11  (0.061) -0.96  (0.062) -0.75  (0.063) -0.83  (0.061) -0.58  (0.086)
Nighttime Change from BL (n=418,413,399,422,198) -0.78  (0.049) -0.63  (0.049) -0.48  (0.050) -0.52  (0.049) -0.34  (0.069)
16.Secondary Outcome
Title Percentage of "Days With no Rescue Medication Use" Over 26 Weeks
Hide Description 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
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Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 418 411 397 419 196
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of days
47.09  (1.752) 44.81  (1.764) 37.74  (1.790) 36.51  (1.752) 34.76  (2.437)
17.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 464 471 464 473 228
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Day 1 1.52  (0.006) 1.46  (0.006) 1.49  (0.006) 1.44  (0.006) 1.30  (0.008)
Week 26 (n=433,418,412,435,186) 1.57  (0.010) 1.46  (0.010) 1.43  (0.010) 1.44  (0.010) 1.23  (0.015)
18.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 64 64 63 70 31
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Day1 1.50  (0.017) 1.40  (0.017) 1.42  (0.018) 1.38  (0.017) 1.24  (0.023)
Week 26 (n=60,55,58,67,27) 1.52  (0.027) 1.39  (0.027) 1.39  (0.028) 1.39  (0.027) 1.18  (0.036)
19.Secondary Outcome
Title Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 60 55 58 67 27
Least Squares Mean (Standard Error)
Unit of Measure: Liters
1.46  (0.026) 1.35  (0.027) 1.35  (0.027) 1.36  (0.026) 1.15  (0.036)
20.Secondary Outcome
Title 24 Hour Holter Monitoring in a Subset of Patients
Hide Description

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
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Hide Analysis Population Description
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/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Placebo
Hide Arm/Group Description:
QVA149 110/50 μg capsules for inhalation delivered once daily via a single-dose dry powder inhaler (SDPPI) 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.
QAB149 150 μg capsules for inhalation delivered once daily via a 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.
NVA237 50 μg capsules for inhalation delivered once daily via a 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.
Matching Placebo capsules for inhalation delivered once daily via a 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.
Overall Number of Participants Analyzed 59 52 55 24
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute
Week 12 (n=35,38,27,15) 80.8  (1.5) 79.9  (1.35) 79.4  (1.57) 78.9  (1.95)
Week 26 (n=36,36,26,16) 79.8  (1.68) 78.6  (1.57) 80.5  (1.75) 77.0  (2.09)
21.Secondary Outcome
Title Rate of Moderate or Severe COPD Exacerbation
Hide Description Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
Time Frame 26 Weeks
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 474 476 473 480 232
Measure Type: Number
Unit of Measure: Exacerbations per year
0.46 0.59 0.52 0.45 0.75
22.Secondary Outcome
Title Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period
Hide Description [Not Specified]
Time Frame 26 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set includes all randomized participants who received at least one dose of study drug.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 474 476 473 480 232
Measure Type: Number
Unit of Measure: Percentage of participants
17.9 21.6 18.8 17.7 25.8
23.Secondary Outcome
Title Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization
Hide Description [Not Specified]
Time Frame 26 Weeks
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Full Analysis Set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
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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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 474 476 473 480 232
Measure Type: Number
Unit of Measure: Percentage of participants
Requiring hospitalization 2.1 2.5 1.9 1.0 3.0
Corticosteroids_Antibiotics-No hospitalization 16.7 19.7 17.8 16.9 23.3
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Hide Arm/Group Description 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. 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. NVA237 50 μg capsules for inhalation delivered once daily via a 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. 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. 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.
All-Cause Mortality
Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
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Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/474 (4.64%)   26/476 (5.46%)   29/473 (6.13%)   19/480 (3.96%)   13/232 (5.60%) 
Blood and lymphatic system disorders           
Anaemia  1  0/474 (0.00%)  1/476 (0.21%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Lymphadenopathy  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Cardiac disorders           
Acute coronary syndrome  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Angina pectoris  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Angina unstable  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Atrial fibrillation  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Bradycardia  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Cardiac arrest  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Cardiac failure  1  0/474 (0.00%)  3/476 (0.63%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Cardiac failure congestive  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  1/480 (0.21%)  0/232 (0.00%) 
Cardio-respiratory arrest  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Cardiomegaly  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Cor pulmonale  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Coronary artery disease  1  0/474 (0.00%)  0/476 (0.00%)  2/473 (0.42%)  0/480 (0.00%)  0/232 (0.00%) 
Coronary artery insufficiency  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Left ventricular dysfunction  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Myocardial infarction  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Supraventricular tachycardia  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Ventricular extrasystoles  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Ear and labyrinth disorders           
Vertigo  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Eye disorders           
Age-related macular degeneration  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Gastrointestinal disorders           
Abdominal hernia  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Abdominal pain upper  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Anal fistula  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Colonic polyp  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Gastrointestinal haemorrhage  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Haemorrhoidal haemorrhage  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Inguinal hernia  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  2/480 (0.42%)  0/232 (0.00%) 
Mesenteric panniculitis  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Oesophageal ulcer  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
General disorders           
Chest pain  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Non-cardiac chest pain  1  1/474 (0.21%)  0/476 (0.00%)  2/473 (0.42%)  1/480 (0.21%)  0/232 (0.00%) 
Temperature intolerance  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Hepatobiliary disorders           
Cholecystitis  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Cholelithiasis  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  2/480 (0.42%)  0/232 (0.00%) 
Infections and infestations           
Bronchitis  1  1/474 (0.21%)  2/476 (0.42%)  3/473 (0.63%)  1/480 (0.21%)  0/232 (0.00%) 
Cellulitis  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Dengue fever  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Empyema  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Gastroenteritis viral  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Herpes zoster  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Injection site abscess  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Liver abscess  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Lobar pneumonia  1  1/474 (0.21%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Lower respiratory tract infection  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Lower respiratory tract infection bacterial  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Moraxella infection  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Oral candidiasis  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Pneumonia  1  2/474 (0.42%)  2/476 (0.42%)  3/473 (0.63%)  3/480 (0.63%)  3/232 (1.29%) 
Respiratory tract infection bacterial  1  2/474 (0.42%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Respiratory tract infection viral  1  1/474 (0.21%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Septic shock  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Upper respiratory tract infection  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Upper respiratory tract infection bacterial  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Urosepsis  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Injury, poisoning and procedural complications           
Contusion  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Fall  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Femoral neck fracture  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Femur fracture  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Hip fracture  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Muscle injury  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Rib fracture  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Spinal compression fracture  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Traumatic intracranial haemorrhage  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Investigations           
Blood albumin decreased  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Prostatic specific antigen increased  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Metabolism and nutrition disorders           
Hyperglycaemia  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Hypokalaemia  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Musculoskeletal and connective tissue disorders           
Back pain  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Osteoporosis  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Bladder cancer  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Brain neoplasm malignant  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Bronchial carcinoma  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Colon cancer  1  1/474 (0.21%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Hepatic neoplasm malignant  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Laryngeal cancer  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Lung neoplasm malignant  1  1/474 (0.21%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Prostate cancer  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Nervous system disorders           
Cerebrovascular accident  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Dizziness  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Syncope  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Transient ischaemic attack  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Psychiatric disorders           
Substance abuse  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Reproductive system and breast disorders           
Benign prostatic hyperplasia  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Breast mass  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Respiratory, thoracic and mediastinal disorders           
Acute respiratory failure  1  1/474 (0.21%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Chronic obstructive pulmonary disease  1  10/474 (2.11%)  15/476 (3.15%)  9/473 (1.90%)  7/480 (1.46%)  7/232 (3.02%) 
Hydrothorax  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  1/480 (0.21%)  0/232 (0.00%) 
Pleural effusion  1  0/474 (0.00%)  1/476 (0.21%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Respiratory failure  1  1/474 (0.21%)  0/476 (0.00%)  2/473 (0.42%)  1/480 (0.21%)  0/232 (0.00%) 
Vascular disorders           
Aortic stenosis  1  0/474 (0.00%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  1/232 (0.43%) 
Arteriosclerosis  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Hypertension  1  0/474 (0.00%)  0/476 (0.00%)  1/473 (0.21%)  0/480 (0.00%)  0/232 (0.00%) 
Peripheral ischaemia  1  1/474 (0.21%)  0/476 (0.00%)  0/473 (0.00%)  0/480 (0.00%)  0/232 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Indacaterol and Glycopyrronium (QVA149) Indacaterol (QAB149) Glycopyrronium (NVA237) Tiotropium Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   166/474 (35.02%)   189/476 (39.71%)   185/473 (39.11%)   172/480 (35.83%)   102/232 (43.97%) 
Infections and infestations           
Nasopharyngitis  1  31/474 (6.54%)  35/476 (7.35%)  46/473 (9.73%)  40/480 (8.33%)  23/232 (9.91%) 
Upper respiratory tract infection  1  20/474 (4.22%)  31/476 (6.51%)  20/473 (4.23%)  24/480 (5.00%)  13/232 (5.60%) 
Upper respiratory tract infection bacterial  1  10/474 (2.11%)  12/476 (2.52%)  15/473 (3.17%)  22/480 (4.58%)  13/232 (5.60%) 
Respiratory, thoracic and mediastinal disorders           
Chronic obstructive pulmonary disease  1  131/474 (27.64%)  144/476 (30.25%)  146/473 (30.87%)  133/480 (27.71%)  87/232 (37.50%) 
Cough  1  26/474 (5.49%)  38/476 (7.98%)  18/473 (3.81%)  21/480 (4.38%)  8/232 (3.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
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Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01202188    
Other Study ID Numbers: CQVA149A2303
2009-017772-25 ( EudraCT Number )
First Submitted: September 13, 2010
First Posted: September 15, 2010
Results First Submitted: February 7, 2013
Results First Posted: May 3, 2013
Last Update Posted: September 9, 2013