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Effect of QVA149 Versus NVA237 and Tiotropium on Chronic Obstructive Pulmonary Disorder (COPD) Exacerbations (SPARK)

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ClinicalTrials.gov Identifier: NCT01120691
Recruitment Status : Completed
First Posted : May 11, 2010
Results First Posted : September 30, 2013
Last Update Posted : December 2, 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
Interventions Drug: QVA149
Drug: NVA237
Drug: tiotropium
Drug: Salbutamol/albuterol
Enrollment 2224
Recruitment Details A total of 3865 participants were screened of whom 2224 were randomized to 1 of the 3 treatment groups (QVA149, NVA237 or tiotropium) in a 1:1:1 ratio for at least 64 weeks (maximum 76 weeks) of treatment period.
Pre-assignment Details 5 (QVA149), 2 (NVA237) and 3 (tiotropium) participants were randomized but did not receive study drug.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period. Salbutamol/albuterol was available for rescue medication use throughout the study. NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period. Salbutamol/albuterol was available for rescue medication use throughout the study. Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Period Title: Overall Study
Started 741 741 742
Full Analysis Set (FAS) 736 739 739
Safety Set (SAF) 736 740 739
Modified Safety Set (mSAF) 729 740 737
Modified Full Analysis Set (mFAS) 729 739 737
Completed 570 538 559
Not Completed 171 203 183
Reason Not Completed
Adverse Event             59             67             47
Subject withdrew consent             33             50             44
Death             21             22             24
Unsatisfactory therapeutic effect             18             32             38
Administrative problems             15             8             9
Protocol deviation             13             12             12
Lost to Follow-up             5             6             4
Abnormal test procedure result(s)             3             2             1
Patient's inability to use the device             3             1             0
Abnormal laboratory value(s)             1             3             4
Arm/Group Title QVA149 NVA237 Open-label Tiotropium Total
Hide Arm/Group Description QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period. Salbutamol/albuterol was available for rescue medication use throughout the study. NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period. Salbutamol/albuterol was available for rescue medication use throughout the study. Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study. Total of all reporting groups
Overall Number of Baseline Participants 729 740 737 2206
Hide Baseline Analysis Population Description
The modified safety set (mSAF set) includes all patients in the safety set except patients from a site who had major GCP issues.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 729 participants 740 participants 737 participants 2206 participants
63.1  (8.07) 63.1  (7.98) 63.6  (7.79) 63.3  (7.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 729 participants 740 participants 737 participants 2206 participants
Female
173
  23.7%
198
  26.8%
184
  25.0%
555
  25.2%
Male
556
  76.3%
542
  73.2%
553
  75.0%
1651
  74.8%
1.Primary Outcome
Title Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and NVA237 Treatment Arms During the Treatment Period.
Hide Description

A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as a worsening of two or more of the following major symptoms for at least 2 consecutive days: dyspnea, sputum volume or sputum purulence OR a worsening of any 1 major symptom together with an increase in any 1 of the following minor symptoms for at least 2 consecutive days: sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough or wheezing. A COPD exacerbation was considered of moderate severity if treatment with systemic glucocorticosteroids or antibiotics or both was required and severe if hospitalization was required. An emergency room (ER) visit of longer than 24 hours was considered a hospitalization.

Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years

Time Frame 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site , which had major issues with Good Clinical Practice (GCP) compliance.
Arm/Group Title QVA149 NVA237
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 739
Overall Number of Units Analyzed
Type of Units Analyzed: Moderate to Severe COPD Exacerbation
812 900
Measure Type: Number
Unit of Measure: Exacerbations per year
0.94 1.07
2.Secondary Outcome
Title Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and Open-label Tiotropium Treatment Arms During the Treatment Period.
Hide Description

A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as a worsening of two or more of the following major symptoms for at least 2 consecutive days: dyspnea, sputum volume or sputum purulence OR a worsening of any 1 major symptom together with an increase in any 1 of the following minor symptoms for at least 2 consecutive days: sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough or wheezing. A COPD exacerbation was considered of moderate severity if treatment with systemic glucocorticosteroids or antibiotics or both was required and severe if hospitalization was required. An emergency room (ER) visit of longer than 24 hours was considered a hospitalization.

Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years

Time Frame 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site, which had major issues with GCP compliance.
Arm/Group Title QVA149 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 737
Overall Number of Units Analyzed
Type of Units Analyzed: Moderate to Severe COPD Exacerbation
812 898
Measure Type: Number
Unit of Measure: Exacerbations per year
0.94 1.06
3.Secondary Outcome
Title Time to First Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Between QVA149, NVA237 and Open Label Tiotropium During the Treatment Period
Hide Description

A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as a worsening of two or more of the following major symptoms for at least 2 consecutive days: dyspnea, sputum volume or sputum purulence OR a worsening of any 1 major symptom together with an increase in any 1 of the following minor symptoms for at least 2 consecutive days: sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough or wheezing. A COPD exacerbation was considered of moderate severity if treatment with systemic glucocorticosteroids or antibiotics or both was required and severe if hospitalization was required. An emergency room (ER) visit of longer than 24 hours was considered a hospitalization.

Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years

Time Frame 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site, which had major issues with GCP compliance. Only patients with a moderate or severe COPD exacerbation were included in this analysis.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 419 426 402
Median (95% Confidence Interval)
Unit of Measure: days
296
(267 to 358)
287
(255 to 325)
331
(280 to 390)
4.Secondary Outcome
Title Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Requiring the Use of Both Systemic Glucocorticosteroids and Antibiotics
Hide Description Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
Time Frame 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site, which had major issues with GCP compliance. The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug and data was available for analysis.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 739 737
Overall Number of Units Analyzed
Type of Units Analyzed: Exacerbations
403 491 461
Measure Type: Number
Unit of Measure: exacerbations per year
0.46 0.58 0.54
5.Secondary Outcome
Title Number of Days With Moderate or Severe Exacerbation That Required Treatment With Systemic Corticosteroids and Antibiotics
Hide Description The number of exacerbation days is defined as the sum of the duration of days recorded as an exacerbation for all exacerbations recorded per patient.
Time Frame 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site with GCP non-compliance. This is a sub-group analysis with mutually exclusive population in each category for analysis.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 528 575 556
Mean (Standard Deviation)
Unit of Measure: Days
systemic corticosteroids [n= 97, 108, 109] 20.49  (25.426) 25.22  (42.674) 17.57  (17.797)
antibiotics [n= 195, 177, 177] 25.08  (47.035) 18.10  (21.790) 25.94  (50.007)
corticosteroids and antibiotic [n= 266, 290, 270] 22.10  (49.999) 26.18  (52.336) 22.03  (42.513)
6.Secondary Outcome
Title Time to Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.) During the Treatment Period.
Hide Description Time to Study Withdrawal or Premature Discontinuation for Any Reason was analyzed for each treatment group using a Kaplan-Meier estimation for the modified safety set. Patients who did not discontinue early were censored at the final visit of the treatment phase.
Time Frame 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified safety set (mSAF set) includes all patients in the safety set except patients from a site who had major GCP issues. The Safety set includes all patients who received at least one dose of study drug whether or not being randomized. Analysis population included patients with study withdrawal or premature discontinuation for any reason.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 159 202 178
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Less than 50% of patients had withdrawn from the study or prematurely discontinued for any reason.
7.Secondary Outcome
Title Percentage of Patients With Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.)During the Treatment Period
Hide Description Percentage of Patients With Study Withdrawal or Premature Discontinuation for Any Reason was analyzed for each treatment group using a Kaplan-Meier estimation for the modified safety set. Patients who did not discontinue early were censored at the final visit of the treatment phase.
Time Frame 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified safety set (mSAF set) includes all patients in the safety set except patients from a site who had major GCP issues. The Safety set includes all patients who received at least one dose of study drug whether or not being randomized
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 740 737
Measure Type: Number
Unit of Measure: percentage of participants
21.8 27.3 24.2
8.Secondary Outcome
Title Cumulative Rates of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations for Multiple COPD Exacerbation at Different Time Points
Hide Description Cumulative rates were estimated using Anderson and Gill method. Chronic Obstructive Pulmonary Disease (COPD) exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if treatment for moderate severity and hospitalization were required. Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
Time Frame 26, 52, 64, 76 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set(mFAS) included all patients in the Full Analysis Set (FAS) except patients from a site, which had major issues with GCP compliance. FAS include all randomized patients who received at least one dose of study drug and data was available for analysis.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks.Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 739 737
Overall Number of Units Analyzed
Type of Units Analyzed: Moderate or Severe COPD Exacerbations
831 926 897
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: exacerbations per year
26 weeks
0.57
(0.51 to 0.62)
0.65
(0.58 to 0.71)
0.63
(0.56 to 0.70)
52 weeks
0.99
(0.91 to 1.09)
1.13
(1.03 to 1.25)
1.11
(1.00 to 1.23)
64 weeks
1.19
(1.08 to 1.30)
1.36
(1.24 to 1.49)
1.31
(1.19 to 1.46)
76 weeks
1.39
(1.27 to 1.53)
1.59
(1.45 to 1.74)
1.55
(1.40 to 1.71)
9.Secondary Outcome
Title Pre-dose Forced Expiratory Volume in 1 Second (FEV-1) After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium
Hide Description

Pulmonary function assessments were performed using centralized spirometry. The spirometer was customized and programmed according to the requirements of the study protocol in accordance with American Thoracic Society (ATS) standards.

Spirometry measurements taken were FEV1 at -45 minutes and -15 minutes pre-dose. Three acceptable maneuvers had to be performed for each time point. The FEV1 values recorded had to be the highest values measured irrespective of whether or not they occurred on the same curve.

The mixed model for analysis contained treatment as a fixed effect with average of the 45 minutes and 15 minutes pre dose FEV1 measurements at day 1 as the baseline measurement, FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at -14 Day) as covariates.

Time Frame 4, 12, 26, 38, 52 and 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set(mFAS) included all patients in the Full Analysis Set (FAS) except patients from a site, which had major issues with GCP compliance. FAS include all randomized patients who received at least one dose of study drug and data was available for analysis. Each category has patients with assessable data at that particular time.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 739 737
Least Squares Mean (Standard Error)
Unit of Measure: L (liters)
predose FEV1 Week 4 (n= 656,654,630) 1.08  (0.009) 0.99  (0.009) 1.00  (0.009)
predose FEV1 Week 12 (n= 666,663,653) 1.08  (0.010) 1.01  (0.009) 1.01  (0.009)
predose FEV1 Week 26 (n= 604,577,599) 1.07  (0.010) 0.99  (0.010) 1.00  (0.010)
predose FEV1 Week 38 (n= 593,549,583) 1.08  (0.011) 1.00  (0.011) 1.00  (0.011)
predose FEV1 Week 52 (n= 557,538,548) 1.05  (0.011) 0.98  (0.011) 0.99  (0.011)
predose FEV1 Week 64 (n= 549,504,530) 1.05  (0.011) 0.98  (0.011) 0.99  (0.011)
10.Secondary Outcome
Title Pre-dose Forced Vital Capacity (FVC)After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium
Hide Description

Pulmonary function assessments were performed using centralized spirometry. The spirometer was customized and programmed according to the requirements of the study protocol in accordance with American Thoracic Society (ATS) standards.

Pre-dose Forced Vital Capacity (FVC) is defined as the average of the -15 minutes and the -45 minutes FVC values. Baseline is defined as the average of the -45 minutes and -15 minutes FVC values taken on day 1 prior to first dose. FVC data taken within 6h of rescue medication or within 7 days of systemic corticosteroid is excluded from this analysis

Time Frame 4, 12, 26, 38, 52 and 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set(mFAS) included all patients in the Full Analysis Set (FAS) except patients from a site, which had major issues with GCP compliance. FAS include all randomized patients who received at least one dose of study drug and data was available for analysis. Each category has patients with assessable data at that particular time.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 739 737
Least Squares Mean (Standard Error)
Unit of Measure: L (liters)
predose FVC Week 4 (n= 656,654,630) 2.74  (0.020) 2.59  (0.019) 2.60  (0.019)
predose FVC Week 12 (n= 623,621,619) 2.77  (0.021) 2.63  (0.021) 2.65  (0.021)
predose FVC Week 26 (n= 604,577,599) 2.73  (0.023) 2.60  (0.022) 2.61  (0.022)
predose FVC Week 38 (n= 592,548,580) 2.76  (0.025) 2.65  (0.025) 2.63  (0.025)
predose FVC Week 52 (n= 557,538,547) 2.68  (0.025) 2.58  (0.025) 2.58  (0.025)
predose FVC Week 64 (n= 549,502,526) 2.67  (0.025) 2.57  (0.025) 2.59  (0.025)
11.Secondary Outcome
Title Change in Mean Daily Use (Number of Puffs) of Rescue Therapy Between QVA149, NVA237 and Open Label Tiotropium From Baseling Over the 64 Week Treatment Period
Hide Description The severe or less FEV1 % predicted (post bronchodilator)>=30%; very severe=> FEV1 % predicted(the post bronchodilator)<30%.Number of puffs of rescue medication taken in the previous 12 hours was recorded 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.
Time Frame Baseline (14 day run-in), 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set mFAS included all patients in the Full analysis set except patients from a site,which had major issues with GCP compliance. The Full Analysis Set includes all randomized patients who received at least one dose of study drug and data was available for analysis. Patients with evaluable data were included in this analysis
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 708 724 709
Least Squares Mean (Standard Error)
Unit of Measure: # puffs
Mean Daily # puffs Severe or Less(n=565,575,561) -2.3  (0.137) -1.5  (0.135) -1.6  (0.136)
Mean Daily # puffs Very Severe (n=143,149,148) -2.1  (0.234) -1.1  (0.228) -1.0  (0.228)
12.Secondary Outcome
Title Change From Baseline of Percentage of Days Without Rescue Therapy Use Between QVA149,NVA237 and Open Label Tiotropium Over the 64 Week Treatment Period
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 Baseline (14 day run-in), 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set(mFAS)included all patients in the Full analysis set except patients from a site,which had major issues with GCP compliance. The Full Analysis Set includes all randomized patients who received at least one dose of study drug and data was available for analysis. Patients with evaluable data were included in this analysis
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 701 720 703
Least Squares Mean (Standard Error)
Unit of Measure: percentage of days
29.36  (1.445) 21.65  (1.410) 23.86  (1.422)
13.Secondary Outcome
Title St. George's Respiratory Questionnaire (SGRQ) Scores Between QVA149, NVA237 and Open Label Tiotropium Over 12, 26, 38, 52 and 64 Weeks of Treatment
Hide Description St. George's Respiratory Questionnaire (SGRQ) is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. Mixed model used baseline SGRQ, baseline inhaled corticosteroid (ICS) use, Forced Expiratory Volume in 1 Second (FEV1) prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates. SGRQ total score is the sum of the scores from the three components; symptoms, activity and impacts.
Time Frame 12, 26, 38, 52 and 64 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site, which had major issues with GCP compliance. The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug and data was available for analysis.
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description:
QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Overall Number of Participants Analyzed 729 739 737
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 12 (n= 694,694,676) 44.69  (0.612) 47.13  (0.603) 47.62  (0.607)
Week 26 (n= 684,677,658) 44.06  (0.655) 45.93  (0.647) 45.77  (0.651)
Week 38 (n= 648,626,635) 42.72  (0.667) 45.53  (0.663) 45.86  (0.660)
Week 52 (n= 625,593,613) 43.38  (0.722) 45.96  (0.723) 46.21  (0.714)
Week 64 (n= 600,564,579) 43.39  (0.778) 45.46  (0.780) 46.08  (0.778)
Time Frame [Not Specified]
Adverse Event Reporting Description Modified safety set (mSAF set) includes all patients in the safety set except patients from a site who had major GCP issues. The Safety set includes all patients who received at least one dose of study drug whether or not being randomized. Analysis population included patients with study withdrawal or premature discontinuation for any reason.
 
Arm/Group Title QVA149 NVA237 Open-label Tiotropium
Hide Arm/Group Description QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study. NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study. Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device. for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
All-Cause Mortality
QVA149 NVA237 Open-label Tiotropium
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
QVA149 NVA237 Open-label Tiotropium
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   167/729 (22.91%)   179/740 (24.19%)   165/737 (22.39%) 
Blood and lymphatic system disorders       
Anaemia  1  2/729 (0.27%)  0/740 (0.00%)  1/737 (0.14%) 
Idiopathic thrombocytopenic purpura  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Cardiac disorders       
Acute coronary syndrome  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Acute myocardial infarction  1  1/729 (0.14%)  4/740 (0.54%)  2/737 (0.27%) 
Angina pectoris  1  1/729 (0.14%)  3/740 (0.41%)  1/737 (0.14%) 
Angina unstable  1  1/729 (0.14%)  2/740 (0.27%)  0/737 (0.00%) 
Arteriosclerosis coronary artery  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Atrial fibrillation  1  6/729 (0.82%)  3/740 (0.41%)  4/737 (0.54%) 
Atrial flutter  1  0/729 (0.00%)  2/740 (0.27%)  1/737 (0.14%) 
Cardiac arrest  1  1/729 (0.14%)  4/740 (0.54%)  2/737 (0.27%) 
Cardiac failure  1  1/729 (0.14%)  1/740 (0.14%)  4/737 (0.54%) 
Cardiac failure acute  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Cardiac failure chronic  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cardiac failure congestive  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Cardio-respiratory arrest  1  1/729 (0.14%)  3/740 (0.41%)  3/737 (0.41%) 
Cardiopulmonary failure  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cor pulmonale  1  0/729 (0.00%)  3/740 (0.41%)  0/737 (0.00%) 
Cor pulmonale chronic  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Coronary artery disease  1  3/729 (0.41%)  2/740 (0.27%)  1/737 (0.14%) 
Ischaemic cardiomyopathy  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Left ventricular dysfunction  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Left ventricular hypertrophy  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Mitral valve incompetence  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Myocardial infarction  1  2/729 (0.27%)  3/740 (0.41%)  4/737 (0.54%) 
Myocardial ischaemia  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Pericardial effusion  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Pericarditis  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Right ventricular failure  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Supraventricular tachyarrhythmia  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Tachycardia  1  0/729 (0.00%)  2/740 (0.27%)  0/737 (0.00%) 
Congenital, familial and genetic disorders       
Congenital laryngeal stridor  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Phimosis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Ear and labyrinth disorders       
Acute vestibular syndrome  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Vertigo  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Endocrine disorders       
Goitre  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Eye disorders       
Angle closure glaucoma  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cataract  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Retinal detachment  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Vision blurred  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Gastrointestinal disorders       
Abdominal distension  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Abdominal pain  1  2/729 (0.27%)  1/740 (0.14%)  1/737 (0.14%) 
Abdominal pain upper  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Colitis ulcerative  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Constipation  1  0/729 (0.00%)  2/740 (0.27%)  0/737 (0.00%) 
Diarrhoea  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Duodenal ulcer  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Duodenal ulcer perforation  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Enteritis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Food poisoning  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Gastric disorder  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Gastric ulcer  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Gastritis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Gastrointestinal haemorrhage  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Gastrooesophageal reflux disease  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Haemorrhoids  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Hiatus hernia  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Inguinal hernia  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Intestinal congestion  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Intestinal obstruction  1  0/729 (0.00%)  2/740 (0.27%)  0/737 (0.00%) 
Intestinal polyp  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Nausea  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Oesophageal ulcer haemorrhage  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Pancreatic mass  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Pancreatitis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Peptic ulcer haemorrhage  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Small intestinal obstruction  1  0/729 (0.00%)  1/740 (0.14%)  1/737 (0.14%) 
General disorders       
Adverse drug reaction  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Chills  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Cyst  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Death  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Generalised oedema  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Multi-organ failure  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Non-cardiac chest pain  1  2/729 (0.27%)  2/740 (0.27%)  3/737 (0.41%) 
Oedema peripheral  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Pyrexia  1  2/729 (0.27%)  1/740 (0.14%)  2/737 (0.27%) 
Sudden cardiac death  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Sudden death  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Thrombosis in device  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Cholecystitis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cholecystitis acute  1  0/729 (0.00%)  1/740 (0.14%)  1/737 (0.14%) 
Cholelithiasis  1  2/729 (0.27%)  0/740 (0.00%)  0/737 (0.00%) 
Hepatitis alcoholic  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Immune system disorders       
Allergy to arthropod sting  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Infections and infestations       
Abscess  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Abscess intestinal  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Abscess rupture  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Anal abscess  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Appendicitis  1  1/729 (0.14%)  2/740 (0.27%)  1/737 (0.14%) 
Appendicitis perforated  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Bronchitis  1  4/729 (0.55%)  2/740 (0.27%)  5/737 (0.68%) 
Bronchopneumonia  1  2/729 (0.27%)  0/740 (0.00%)  1/737 (0.14%) 
Cellulitis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cholecystitis infective  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Haemophilus infection  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Herpes zoster  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Kidney infection  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Laryngitis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Lobar pneumonia  1  4/729 (0.55%)  2/740 (0.27%)  0/737 (0.00%) 
Lower respiratory tract infection  1  14/729 (1.92%)  24/740 (3.24%)  13/737 (1.76%) 
Lower respiratory tract infection bacterial  1  2/729 (0.27%)  5/740 (0.68%)  1/737 (0.14%) 
Lower respiratory tract infection fungal  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Lower respiratory tract infection viral  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Lung infection  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Lung infection pseudomonal  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Nasopharyngitis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Oral candidiasis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Oropharyngeal candidiasis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Otitis media acute  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Otitis media chronic  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Perineal abscess  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Peritonitis  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Pneumonia  1  23/729 (3.16%)  25/740 (3.38%)  24/737 (3.26%) 
Pneumonia bacterial  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Pneumonia legionella  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Pneumonia primary atypical  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Pneumonia staphylococcal  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Pulmonary tuberculosis  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Rabies  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Respiratory tract infection  1  2/729 (0.27%)  2/740 (0.27%)  0/737 (0.00%) 
Respiratory tract infection bacterial  1  0/729 (0.00%)  2/740 (0.27%)  2/737 (0.27%) 
Respiratory tract infection viral  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Scrotal abscess  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Sepsis  1  1/729 (0.14%)  3/740 (0.41%)  0/737 (0.00%) 
Septic shock  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Subcutaneous abscess  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Upper respiratory tract infection  1  2/729 (0.27%)  0/740 (0.00%)  0/737 (0.00%) 
Upper respiratory tract infection bacterial  1  20/729 (2.74%)  20/740 (2.70%)  10/737 (1.36%) 
Urinary tract infection  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Viral upper respiratory tract infection  1  6/729 (0.82%)  5/740 (0.68%)  3/737 (0.41%) 
Injury, poisoning and procedural complications       
Alcohol poisoning  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Animal bite  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cervical vertebral fracture  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Clavicle fracture  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Contusion  1  0/729 (0.00%)  1/740 (0.14%)  1/737 (0.14%) 
Fall  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Femur fracture  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Head injury  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Hip fracture  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Incisional hernia  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Lower limb fracture  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Meniscus lesion  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Muscle rupture  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Pneumothorax traumatic  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Postoperative ileus  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Rib fracture  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Spinal fracture  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Tendon rupture  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Wound dehiscence  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Wrist fracture  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Investigations       
Blood pressure increased  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Electrocardiogram abnormal  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Intraocular pressure increased  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Metabolism and nutrition disorders       
Cachexia  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Decreased appetite  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Dehydration  1  0/729 (0.00%)  2/740 (0.27%)  0/737 (0.00%) 
Hyperglycaemia  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Hyperkalaemia  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Hypokalaemia  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Hyponatraemia  1  3/729 (0.41%)  1/740 (0.14%)  1/737 (0.14%) 
Malnutrition  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Type 2 diabetes mellitus  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Arthritis  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Back pain  1  1/729 (0.14%)  1/740 (0.14%)  1/737 (0.14%) 
Bursitis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Compartment syndrome  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Intervertebral disc protrusion  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Musculoskeletal pain  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Osteoarthritis  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Osteochondritis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Rhabdomyolysis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Spinal column stenosis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acute myeloid leukaemia  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Adrenal neoplasm  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
B-cell lymphoma  1  0/729 (0.00%)  2/740 (0.27%)  0/737 (0.00%) 
Bladder cancer  1  0/729 (0.00%)  1/740 (0.14%)  1/737 (0.14%) 
Bladder neoplasm  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Breast cancer  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Breast cancer recurrent  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Bronchial carcinoma  1  1/729 (0.14%)  0/740 (0.00%)  2/737 (0.27%) 
Carcinoid tumour of the caecum  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Colon adenoma  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Colon cancer  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Gliosarcoma  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Laryngeal cancer  1  1/729 (0.14%)  0/740 (0.00%)  2/737 (0.27%) 
Laryngeal cancer stage 0  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Lung neoplasm  1  1/729 (0.14%)  2/740 (0.27%)  0/737 (0.00%) 
Lung neoplasm malignant  1  3/729 (0.41%)  0/740 (0.00%)  4/737 (0.54%) 
Lung squamous cell carcinoma stage unspecified  1  1/729 (0.14%)  1/740 (0.14%)  1/737 (0.14%) 
Mediastinum neoplasm  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Metastases to bone  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Metastases to central nervous system  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Metastases to liver  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Metastases to lung  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Non-small cell lung cancer  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Oesophageal carcinoma  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Oesophageal squamous cell carcinoma  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Pancreatic neoplasm  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Prostate cancer  1  0/729 (0.00%)  2/740 (0.27%)  0/737 (0.00%) 
Prostatic adenoma  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Rectal cancer  1  0/729 (0.00%)  1/740 (0.14%)  2/737 (0.27%) 
Renal cancer  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Small cell lung cancer metastatic  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Small intestine carcinoma  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Squamous cell carcinoma  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Nervous system disorders       
Ataxia  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cerebellar syndrome  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Cerebral haemorrhage  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Cerebral infarction  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Cerebral ischaemia  1  2/729 (0.27%)  0/740 (0.00%)  0/737 (0.00%) 
Cerebrovascular accident  1  1/729 (0.14%)  1/740 (0.14%)  3/737 (0.41%) 
Cerebrovascular disorder  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Cerebrovascular insufficiency  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Cervicobrachial syndrome  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Convulsion  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Epilepsy  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Grand mal convulsion  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Headache  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Ischaemic stroke  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Lethargy  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Loss of consciousness  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Monoparesis  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Movement disorder  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Neuropathy peripheral  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Syncope  1  3/729 (0.41%)  0/740 (0.00%)  0/737 (0.00%) 
Transient ischaemic attack  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Psychiatric disorders       
Alcohol withdrawal syndrome  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Completed suicide  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Confusional state  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Delirium  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Depression  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Hallucination  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Major depression  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Mental status changes  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Psychotic disorder  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Renal and urinary disorders       
Acute prerenal failure  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Bladder dysfunction  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Calculus ureteric  1  0/729 (0.00%)  2/740 (0.27%)  0/737 (0.00%) 
Nephrolithiasis  1  2/729 (0.27%)  0/740 (0.00%)  0/737 (0.00%) 
Renal colic  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Urinary retention  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  2/729 (0.27%)  1/740 (0.14%)  1/737 (0.14%) 
Epididymitis  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory distress syndrome  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Acute respiratory failure  1  7/729 (0.96%)  6/740 (0.81%)  1/737 (0.14%) 
Atelectasis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Chronic obstructive pulmonary disease  1  107/729 (14.68%)  116/740 (15.68%)  87/737 (11.80%) 
Chronic respiratory failure  1  1/729 (0.14%)  1/740 (0.14%)  0/737 (0.00%) 
Cough  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Dyspnoea  1  5/729 (0.69%)  2/740 (0.27%)  3/737 (0.41%) 
Epistaxis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Foreign body aspiration  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Haemoptysis  1  1/729 (0.14%)  2/740 (0.27%)  1/737 (0.14%) 
Hydrothorax  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Hypercapnia  1  0/729 (0.00%)  3/740 (0.41%)  1/737 (0.14%) 
Hypoxia  1  1/729 (0.14%)  1/740 (0.14%)  1/737 (0.14%) 
Lung consolidation  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Lung disorder  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Oropharyngeal pain  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Pleural effusion  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Pleurisy  1  0/729 (0.00%)  1/740 (0.14%)  1/737 (0.14%) 
Pneumothorax  1  0/729 (0.00%)  5/740 (0.68%)  1/737 (0.14%) 
Productive cough  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Pulmonary air leakage  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Pulmonary congestion  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Pulmonary embolism  1  3/729 (0.41%)  3/740 (0.41%)  1/737 (0.14%) 
Pulmonary hypertension  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Pulmonary mass  1  0/729 (0.00%)  0/740 (0.00%)  2/737 (0.27%) 
Respiratory distress  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Respiratory failure  1  5/729 (0.69%)  7/740 (0.95%)  6/737 (0.81%) 
Sleep apnoea syndrome  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Sputum increased  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Vocal cord inflammation  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Wheezing  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Skin and subcutaneous tissue disorders       
Angioedema  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Dermal cyst  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Social circumstances       
Pollution  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Surgical and medical procedures       
Coronary arterial stent insertion  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Vascular disorders       
Aortic aneurysm  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Aortic aneurysm rupture  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Arterial occlusive disease  1  0/729 (0.00%)  0/740 (0.00%)  2/737 (0.27%) 
Arterial stenosis  1  0/729 (0.00%)  1/740 (0.14%)  0/737 (0.00%) 
Arteriosclerosis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Deep vein thrombosis  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Hypertension  1  2/729 (0.27%)  2/740 (0.27%)  2/737 (0.27%) 
Hypotension  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Iliac artery stenosis  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Peripheral arterial occlusive disease  1  1/729 (0.14%)  0/740 (0.00%)  1/737 (0.14%) 
Peripheral artery aneurysm  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Peripheral ischaemia  1  0/729 (0.00%)  0/740 (0.00%)  1/737 (0.14%) 
Phlebitis deep  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Shock haemorrhagic  1  1/729 (0.14%)  0/740 (0.00%)  0/737 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
QVA149 NVA237 Open-label Tiotropium
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   656/729 (89.99%)   671/740 (90.68%)   666/737 (90.37%) 
Cardiac disorders       
Tachycardia  1  3/729 (0.41%)  8/740 (1.08%)  3/737 (0.41%) 
Gastrointestinal disorders       
Abdominal pain  1  6/729 (0.82%)  11/740 (1.49%)  9/737 (1.22%) 
Abdominal pain upper  1  7/729 (0.96%)  7/740 (0.95%)  8/737 (1.09%) 
Constipation  1  8/729 (1.10%)  11/740 (1.49%)  4/737 (0.54%) 
Diarrhoea  1  21/729 (2.88%)  11/740 (1.49%)  15/737 (2.04%) 
Dry mouth  1  4/729 (0.55%)  13/740 (1.76%)  16/737 (2.17%) 
Dyspepsia  1  13/729 (1.78%)  10/740 (1.35%)  15/737 (2.04%) 
Gastritis  1  12/729 (1.65%)  5/740 (0.68%)  12/737 (1.63%) 
Gastrooesophageal reflux disease  1  9/729 (1.23%)  4/740 (0.54%)  9/737 (1.22%) 
Nausea  1  9/729 (1.23%)  12/740 (1.62%)  4/737 (0.54%) 
Toothache  1  9/729 (1.23%)  4/740 (0.54%)  6/737 (0.81%) 
General disorders       
Fatigue  1  4/729 (0.55%)  8/740 (1.08%)  3/737 (0.41%) 
Non-cardiac chest pain  1  14/729 (1.92%)  11/740 (1.49%)  9/737 (1.22%) 
Oedema peripheral  1  22/729 (3.02%)  18/740 (2.43%)  16/737 (2.17%) 
Pyrexia  1  26/729 (3.57%)  24/740 (3.24%)  22/737 (2.99%) 
Infections and infestations       
Bronchitis  1  32/729 (4.39%)  36/740 (4.86%)  26/737 (3.53%) 
Influenza  1  23/729 (3.16%)  22/740 (2.97%)  19/737 (2.58%) 
Lower respiratory tract infection  1  49/729 (6.72%)  68/740 (9.19%)  69/737 (9.36%) 
Lower respiratory tract infection bacterial  1  6/729 (0.82%)  8/740 (1.08%)  4/737 (0.54%) 
Nasopharyngitis  1  98/729 (13.44%)  81/740 (10.95%)  90/737 (12.21%) 
Oral candidiasis  1  11/729 (1.51%)  10/740 (1.35%)  12/737 (1.63%) 
Pharyngitis  1  17/729 (2.33%)  11/740 (1.49%)  10/737 (1.36%) 
Pneumonia  1  11/729 (1.51%)  13/740 (1.76%)  10/737 (1.36%) 
Rhinitis  1  9/729 (1.23%)  10/740 (1.35%)  6/737 (0.81%) 
Sinusitis  1  12/729 (1.65%)  20/740 (2.70%)  21/737 (2.85%) 
Upper respiratory tract infection  1  26/729 (3.57%)  25/740 (3.38%)  28/737 (3.80%) 
Upper respiratory tract infection bacterial  1  119/729 (16.32%)  123/740 (16.62%)  109/737 (14.79%) 
Urinary tract infection  1  27/729 (3.70%)  19/740 (2.57%)  15/737 (2.04%) 
Viral upper respiratory tract infection  1  70/729 (9.60%)  75/740 (10.14%)  72/737 (9.77%) 
Injury, poisoning and procedural complications       
Contusion  1  9/729 (1.23%)  4/740 (0.54%)  4/737 (0.54%) 
Metabolism and nutrition disorders       
Hypercholesterolaemia  1  14/729 (1.92%)  11/740 (1.49%)  11/737 (1.49%) 
Hyperlipidaemia  1  9/729 (1.23%)  4/740 (0.54%)  7/737 (0.95%) 
Type 2 diabetes mellitus  1  12/729 (1.65%)  9/740 (1.22%)  5/737 (0.68%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  12/729 (1.65%)  10/740 (1.35%)  10/737 (1.36%) 
Back pain  1  24/729 (3.29%)  33/740 (4.46%)  36/737 (4.88%) 
Muscle spasms  1  5/729 (0.69%)  9/740 (1.22%)  9/737 (1.22%) 
Musculoskeletal pain  1  12/729 (1.65%)  9/740 (1.22%)  6/737 (0.81%) 
Pain in extremity  1  9/729 (1.23%)  8/740 (1.08%)  5/737 (0.68%) 
Nervous system disorders       
Dizziness  1  13/729 (1.78%)  12/740 (1.62%)  8/737 (1.09%) 
Headache  1  30/729 (4.12%)  33/740 (4.46%)  39/737 (5.29%) 
Psychiatric disorders       
Depression  1  4/729 (0.55%)  2/740 (0.27%)  9/737 (1.22%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  618/729 (84.77%)  639/740 (86.35%)  629/737 (85.35%) 
Cough  1  40/729 (5.49%)  39/740 (5.27%)  25/737 (3.39%) 
Dysphonia  1  2/729 (0.27%)  5/740 (0.68%)  9/737 (1.22%) 
Dyspnoea  1  21/729 (2.88%)  42/740 (5.68%)  32/737 (4.34%) 
Oropharyngeal pain  1  25/729 (3.43%)  32/740 (4.32%)  29/737 (3.93%) 
Sputum increased  1  7/729 (0.96%)  13/740 (1.76%)  8/737 (1.09%) 
Wheezing  1  5/729 (0.69%)  9/740 (1.22%)  3/737 (0.41%) 
Vascular disorders       
Hypertension  1  30/729 (4.12%)  20/740 (2.70%)  24/737 (3.26%) 
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 or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01120691     History of Changes
Other Study ID Numbers: CQVA149A2304
2009-013256-69 ( EudraCT Number )
First Submitted: May 5, 2010
First Posted: May 11, 2010
Results First Submitted: July 9, 2013
Results First Posted: September 30, 2013
Last Update Posted: December 2, 2013