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Trial record 12 of 538 for:    Argentina | Bulgaria

QVA vs. Salmeterol/Fluticasone, 52-week Exacerbation Study, FLAME (EFfect of Indacaterol Glycopyronium Vs Fluticasone Salmeterol on COPD Exacerbations)

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ClinicalTrials.gov Identifier: NCT01782326
Recruitment Status : Completed
First Posted : February 1, 2013
Results First Posted : May 16, 2016
Last Update Posted : May 16, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: QVA149
Drug: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)
Enrollment 3362
Recruitment Details  
Pre-assignment Details  
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description QVA149 (110/50 μg) once daily Salmeterol/fluticasone (50/500μg) twice a day
Period Title: Planned Treatment Epoch
Started 1680 1682
Full Analysis Set (FAS) 1675 1679
Per-protocol Set (PPS) 1528 1556
Serial Spirometry Set 280 279
Safety Set (SAF) 1678 1680
Urine Cortisol Set 266 269
Completed 1478 1474
Not Completed 202 208
Reason Not Completed
Subject/guardian decision             149             151
Death             29             30
Physician Decision             18             16
Protocol deviation             2             3
Lost to Follow-up             4             4
Technical problems             0             4
Period Title: Double-blind Treatment
Started 1678 1680
Completed 1400 1360
Not Completed 278 320
Reason Not Completed
Adverse Event             129             145
Subject/guardian decision             111             125
Lack of Efficacy             17             22
Physician Decision             13             16
Protocol deviation             8             7
Technical problems             0             5
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS) Total
Hide Arm/Group Description QVA149 (110/50 μg) once daily Salmeterol/fluticasone (50/500μg) twice a day Total of all reporting groups
Overall Number of Baseline Participants 1680 1682 3362
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1680 participants 1682 participants 3362 participants
64.6  (7.89) 64.5  (7.70) 64.6  (7.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1680 participants 1682 participants 3362 participants
Female
381
  22.7%
424
  25.2%
805
  23.9%
Male
1299
  77.3%
1258
  74.8%
2557
  76.1%
1.Primary Outcome
Title Rate of COPD Exacerbations
Hide Description COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event. Estimates are from a generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. As the offset variable log(exposure time in years) was used.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Only PPS patients with non-missing values for all terms in negative binomial model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1528 1556
Least Squares Mean (95% Confidence Interval)
Unit of Measure: COPD Exacerbations/year
3.59
(3.28 to 3.94)
4.03
(3.68 to 4.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Study was designed to have >95% power to rule out a 1.15-fold increase in the rate exacerbations for QVA149 vs. salmeterol/fluticasone.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Generalized linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.83 to 0.96
Estimation Comments If the upper limit of the confidence interval was <1.15 then non-inferiority of QVA149 compared to SFC could be claimed
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Generalized linear method
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.83 to 0.96
Estimation Comments If non-inferiority was demonstrated, superiority of QVA149A compared to SFC in reducing exacerbation rate could be claimed if the upper limit of the same CI was less than 1.
2.Secondary Outcome
Title Time to First COPD Exacerbation.
Hide Description First COPD exacerbations starting between first dose and one day after last treatment are included. Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in Cox regression model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Median (95% Confidence Interval)
Unit of Measure: Days
71.0
(60.0 to 82.0)
51.0
(46.0 to 57.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.78 to 0.91
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Rate of Moderate to Severe COPD Exacerbations.
Hide Description COPD exacerbations starting between date of first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event with the worst severity. A COPD exacerbation of moderate severity meets the symptoms definition in the protocol and requires treatment with systemic corticosteroids and/or antibiotics. A severe COPD exacerbation requires hospitalization. Estimates are from a generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in negative binomial model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1651 1656
Least Squares Mean (95% Confidence Interval)
Unit of Measure: COPD Exacerbation/year
0.98
(0.88 to 1.10)
1.19
(1.07 to 1.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.75 to 0.91
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to First Moderate to Severe COPD Exacerbation.
Hide Description First COPD exacerbations starting between first dose and one day after last treatment are included. Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region.
Time Frame 52 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in the Cox regression model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
308.0
(283.0 to 352.0)
[1]
NA -Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.70 to 0.86
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids
Hide Description COPD exacerbations starting between date of first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event with the worst severity. Estimates are from a generalized linear model assuming a negative binomial distribution with fixed effects of treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in negative binomial model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1651 1656
Least Squares Mean (95% Confidence Interval)
Unit of Measure: COPD Exacerbation/year
0.18
(0.14 to 0.22)
0.18
(0.14 to 0.23)
6.Secondary Outcome
Title Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics
Hide Description Estimates are from a generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used. COPD exacerbations starting between first dose and one day after last treatment are included .
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug. Only FAS patients with non-missing values for all terms in negative binomial model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1651 1656
Least Squares Mean (95% Confidence Interval)
Unit of Measure: COPD Exacerbation/year
0.17
(0.13 to 0.22)
0.22
(0.17 to 0.28)
7.Secondary Outcome
Title Rate of Moderate to Severe COPD Exacerbations Requiring Hospitalization. COPD Exacerbations Starting Between First Dose and One Day After Last Treatment Are Included.
Hide Description All exacerbations requiring hospitalization are considered severe according to protocol definitions so this is the rate of severe COPD exacerbations only. Note - an ER visit of longer than 24 hours was considered a hospitalization.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in negative binomial model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1651 1656
Least Squares Mean (95% Confidence Interval)
Unit of Measure: COPD Exacerbation/year
0.15
(0.11 to 0.19)
0.17
(0.13 to 0.22)
8.Secondary Outcome
Title Rate of Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days
Hide Description Re-hospitalizations are defined as hospitalizations starting within the first 30 days after a severe COPD exacerbation and between first dose and one day after date of last treatment. Generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used. COPD exacerbations starting between first dose and one day after last treatment are included.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in negative binomial model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Mean (Standard Deviation)
Unit of Measure: COPD Exacerbation/year
0.0  (0.15) 0.0  (0.12)
9.Secondary Outcome
Title Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids
Hide Description Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in Cox regression model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.256
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.74 to 1.08
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics
Hide Description Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in Cox regression model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA- Parameters not estimated, data did not reach median
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.69 to 0.95
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Time to First Moderate to Severe COPD Exacerbations Requiring Hospitalization
Hide Description Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in Cox regression model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.66 to 1.00
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Time to First Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days
Hide Description Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in Cox regression model are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.790
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.38 to 2.10
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Forced Expiratory Volume in 1 Second
Hide Description Change from baseline. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, region, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.
Time Frame Baseline, day 1 (30 min and one hour post dose)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and did not have any major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Day 1, 30 min post-dose (n=1659, 1663) 0.121  (0.0049) 0.076  (0.0049)
Day 1, one hour post-dose (n=1657, 1664) 0.147  (0.0054) 0.092  (0.0054)
14.Secondary Outcome
Title Forced Expiratory Volume in 1 Second
Hide Description Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.
Time Frame Baseline, 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1597 1595
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.079  (0.0070) 0.006  (0.0070)
15.Secondary Outcome
Title Forced Expiratory Volume in 1 Second
Hide Description Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.
Time Frame Baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1597 1595
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.070  (0.0072) -0.008  (0.0072)
16.Secondary Outcome
Title Forced Expiratory Volume in 1 Second
Hide Description Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.
Time Frame Baseline, 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1597 1595
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.049  (0.0073) -0.037  (0.0074)
17.Secondary Outcome
Title Forced Expiratory Volume in 1 Second
Hide Description Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.
Time Frame Baseline, 38 weeks
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The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1597 1595
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.034  (0.0074) -0.039  (0.0075)
18.Secondary Outcome
Title Forced Expiratory Volume in 1 Second
Hide Description Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.
Time Frame Baseline, 52 weeks
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Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1597 1595
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.015  (0.0075) -0.048  (0.0076)
19.Secondary Outcome
Title Change From Baseline in Forced Expiratory Volume in 1 Second AUC (0-12h)
Hide Description Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time”
Time Frame Baseline, 52 weeks
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Serial spirometry set - Serial spirometry set includes the patients who performed additional serial spirometry, a subset of FAS. Only patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 279 277
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.078  (0.0174) -0.032  (0.0176)
20.Secondary Outcome
Title Change From Baseline in Total St. George's Respiratory Questionnaire Score
Hide Description The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.
Time Frame Baseline, 4 weeks
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Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1602 1593
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-2.3  (0.36) -2.3  (0.36)
21.Secondary Outcome
Title Change From Baseline in Total St. George's Respiratory Questionnaire Score
Hide Description The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.
Time Frame Baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1602 1593
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-3.2  (0.38) -1.9  (0.38)
22.Secondary Outcome
Title Change From Baseline in Total St. George's Respiratory Questionnaire Score
Hide Description The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.
Time Frame Baseline, 26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1602 1593
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-3.5  (0.39) -2.3  (0.39)
23.Secondary Outcome
Title Change From Baseline in Total St. George's Respiratory Questionnaire Score
Hide Description The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.
Time Frame Baseline, 38 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1602 1593
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-3.5  (0.40) -1.7  (0.40)
24.Secondary Outcome
Title Change From Baseline in Total St. George's Respiratory Questionnaire Score
Hide Description The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1602 1593
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-3.1  (0.41) -1.9  (0.41)
25.Secondary Outcome
Title Change From Baseline in the Number of Puffs of Rescue Medication
Hide Description A linear mixed model (LMM) was used for this analysis Change from baseline in mean number of puffs. LMM including: treatment, baseline value, smoking status at screening, ICS use at screening, airflow limitation severity, region and random effect of center nested within region.
Time Frame Baseline, 52 weeks
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Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug. Only FAS patients with non-missing values for all terms in LLM are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1675 1679
Least Squares Mean (Standard Error)
Unit of Measure: Number of puffs per day
-1.01  (0.097) -0.76  (0.097)
26.Secondary Outcome
Title Change From Baseline in the Safety of QVA149 ((110/50 μg o.d.) vs Fluticasone/Salmeterol (500/50μg Bid) in Terms of HPA Axis Function, as Determined by Collection of 24-hour Urine Cortisol.
Hide Description Urine cortisol/creatinine ratio
Time Frame Baseline, 52 Weeks
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Hide Analysis Population Description
Urine cortisol set is the subset of patients who were measured with 24-hour Urine cortisol, a subset of safety set. The safety set included all patients who received at least one dose of study drug. At the post-baseline timepoint only patients with a value at both baseline and the post-baseline timepoint are included.
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 162 154
Median (Full Range)
Unit of Measure: ng/mL
5.615
(-96.93 to 509.17)
-10.390
(-97.76 to 4444.65)
27.Secondary Outcome
Title Change From Baseline in Forced Vital Capacity
Hide Description Change from baseline in trough value (average of values measured 45 and 15 minutes prior to the morning dose). Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FVC measurements, smoking status at screening, screening inhaled corticosteroid (ICS) use, region, baseline FVC * visit interaction, and visit, treatment * visit interaction
Time Frame 4 Weeks, 12 Weeks, 26 Weeks, 38 Weeks, 52 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least one dose of study drug and had no major GCP violations. Only FAS patients with non-missing values for all terms in MMRM are included
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1597 1595
Least Squares Mean (Standard Error)
Unit of Measure: Liters
4 weeks 0.146  (0.0127) -0.032  (0.0128)
12 weeks 0.134  (0.0131) -0.071  (0.0131)
26 weeks 0.088  (0.0135) -0.121  (0.0136)
38 weeks 0.071  (0.0137) -0.111  (0.0137)
52 weeks 0.022  (0.0139) -0.138  (0.0140)
28.Secondary Outcome
Title Number of Patients With Adverse Events, Serious Adverse Events, and Death
Hide Description The overall rate of adverse events reported from initiation through 30 days post last dose.
Time Frame 52 weeks of treatment + 30 days
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The Safety set:all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received. The statement that a patient had no AEs also constituted a safety assessment. Only deaths occurring on treatment + 30 days after end of treatment were included
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description:
QVA149 (110/50 μg) once daily
Salmeterol/fluticasone (50/500μg) twice a day
Overall Number of Participants Analyzed 1678 1680
Measure Type: Number
Unit of Measure: Number of participants
Patients with at least one SAEs 308 334
Patients with at least one AE 1459 1498
Death 24 24
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Hide Arm/Group Description QVA149 (110/50 μg) once daily Salmeterol/fluticasone (50/500μg) twice a day
All-Cause Mortality
QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
QVA149 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Affected / at Risk (%) Affected / at Risk (%)
Total   308/1678 (18.36%)   334/1680 (19.88%) 
Blood and lymphatic system disorders     
ANAEMIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
HEPARIN-INDUCED THROMBOCYTOPENIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
HYPOCHROMIC ANAEMIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
Cardiac disorders     
ACUTE CORONARY SYNDROME  1  1/1678 (0.06%)  2/1680 (0.12%) 
ACUTE MYOCARDIAL INFARCTION  1  4/1678 (0.24%)  2/1680 (0.12%) 
ANGINA PECTORIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
ANGINA UNSTABLE  1  0/1678 (0.00%)  1/1680 (0.06%) 
ARRHYTHMIA  1  1/1678 (0.06%)  1/1680 (0.06%) 
ATRIAL FIBRILLATION  1  5/1678 (0.30%)  7/1680 (0.42%) 
ATRIAL FLUTTER  1  2/1678 (0.12%)  3/1680 (0.18%) 
ATRIAL TACHYCARDIA  1  2/1678 (0.12%)  0/1680 (0.00%) 
BRADYCARDIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
CARDIAC ARREST  1  5/1678 (0.30%)  1/1680 (0.06%) 
CARDIAC FAILURE  1  5/1678 (0.30%)  7/1680 (0.42%) 
CARDIAC FAILURE ACUTE  1  0/1678 (0.00%)  2/1680 (0.12%) 
CARDIAC FAILURE CONGESTIVE  1  1/1678 (0.06%)  3/1680 (0.18%) 
CARDIAC TAMPONADE  1  0/1678 (0.00%)  1/1680 (0.06%) 
CARDIO-RESPIRATORY ARREST  1  1/1678 (0.06%)  3/1680 (0.18%) 
CARDIOVASCULAR DISORDER  1  1/1678 (0.06%)  0/1680 (0.00%) 
CONGESTIVE CARDIOMYOPATHY  1  1/1678 (0.06%)  0/1680 (0.00%) 
COR PULMONALE  1  0/1678 (0.00%)  2/1680 (0.12%) 
COR PULMONALE CHRONIC  1  0/1678 (0.00%)  2/1680 (0.12%) 
CORONARY ARTERY DISEASE  1  2/1678 (0.12%)  1/1680 (0.06%) 
CORONARY ARTERY STENOSIS  1  1/1678 (0.06%)  2/1680 (0.12%) 
ISCHAEMIC CARDIOMYOPATHY  1  1/1678 (0.06%)  0/1680 (0.00%) 
LEFT VENTRICULAR DYSFUNCTION  1  0/1678 (0.00%)  1/1680 (0.06%) 
LEFT VENTRICULAR FAILURE  1  1/1678 (0.06%)  0/1680 (0.00%) 
MYOCARDIAL INFARCTION  1  6/1678 (0.36%)  5/1680 (0.30%) 
MYOCARDIAL ISCHAEMIA  1  1/1678 (0.06%)  2/1680 (0.12%) 
MYOCARDIAL RUPTURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
PERICARDIAL EFFUSION  1  0/1678 (0.00%)  1/1680 (0.06%) 
PERICARDIAL HAEMORRHAGE  1  1/1678 (0.06%)  0/1680 (0.00%) 
RIGHT VENTRICULAR FAILURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
SINUS TACHYCARDIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
VENTRICULAR ARRHYTHMIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
Congenital, familial and genetic disorders     
PROGRESSIVE CEREBELLAR DEGENERATION  1  1/1678 (0.06%)  0/1680 (0.00%) 
Endocrine disorders     
GOITRE  1  1/1678 (0.06%)  1/1680 (0.06%) 
Eye disorders     
ANGLE CLOSURE GLAUCOMA  1  0/1678 (0.00%)  1/1680 (0.06%) 
OPHTHALMOPLEGIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
OPTIC ISCHAEMIC NEUROPATHY  1  0/1678 (0.00%)  1/1680 (0.06%) 
RETINAL DETACHMENT  1  1/1678 (0.06%)  1/1680 (0.06%) 
Gastrointestinal disorders     
ABDOMINAL DISTENSION  1  0/1678 (0.00%)  1/1680 (0.06%) 
ABDOMINAL HERNIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
ABDOMINAL PAIN UPPER  1  1/1678 (0.06%)  0/1680 (0.00%) 
ACID PEPTIC DISEASE  1  1/1678 (0.06%)  0/1680 (0.00%) 
ASCITES  1  1/1678 (0.06%)  0/1680 (0.00%) 
COLITIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
CONSTIPATION  1  1/1678 (0.06%)  0/1680 (0.00%) 
DIARRHOEA  1  1/1678 (0.06%)  0/1680 (0.00%) 
DUODENAL ULCER  1  1/1678 (0.06%)  0/1680 (0.00%) 
DYSPHAGIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
FAECALOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
GASTRIC ULCER  1  1/1678 (0.06%)  1/1680 (0.06%) 
GASTRITIS  1  0/1678 (0.00%)  2/1680 (0.12%) 
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/1678 (0.00%)  3/1680 (0.18%) 
HAEMATEMESIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
ILEUS  1  0/1678 (0.00%)  1/1680 (0.06%) 
ILEUS PARALYTIC  1  1/1678 (0.06%)  0/1680 (0.00%) 
INGUINAL HERNIA  1  1/1678 (0.06%)  1/1680 (0.06%) 
INTESTINAL PERFORATION  1  1/1678 (0.06%)  0/1680 (0.00%) 
INTESTINAL STENOSIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
LARGE INTESTINE POLYP  1  0/1678 (0.00%)  4/1680 (0.24%) 
NAUSEA  1  0/1678 (0.00%)  1/1680 (0.06%) 
OESOPHAGITIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
PANCREATITIS  1  2/1678 (0.12%)  0/1680 (0.00%) 
PANCREATITIS ACUTE  1  1/1678 (0.06%)  3/1680 (0.18%) 
STOMATITIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
UMBILICAL HERNIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
VOMITING  1  0/1678 (0.00%)  1/1680 (0.06%) 
General disorders     
ASTHENIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
FATIGUE  1  1/1678 (0.06%)  0/1680 (0.00%) 
LOCAL SWELLING  1  1/1678 (0.06%)  0/1680 (0.00%) 
MULTI-ORGAN FAILURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
NON-CARDIAC CHEST PAIN  1  1/1678 (0.06%)  2/1680 (0.12%) 
OEDEMA PERIPHERAL  1  1/1678 (0.06%)  1/1680 (0.06%) 
PYREXIA  1  1/1678 (0.06%)  2/1680 (0.12%) 
SUDDEN CARDIAC DEATH  1  1/1678 (0.06%)  1/1680 (0.06%) 
SUDDEN DEATH  1  1/1678 (0.06%)  2/1680 (0.12%) 
Hepatobiliary disorders     
CHOLECYSTITIS  1  0/1678 (0.00%)  2/1680 (0.12%) 
CHOLELITHIASIS  1  1/1678 (0.06%)  1/1680 (0.06%) 
DRUG-INDUCED LIVER INJURY  1  0/1678 (0.00%)  1/1680 (0.06%) 
HEPATIC CIRRHOSIS  1  2/1678 (0.12%)  0/1680 (0.00%) 
HEPATIC CYST RUPTURED  1  0/1678 (0.00%)  1/1680 (0.06%) 
HEPATIC FUNCTION ABNORMAL  1  1/1678 (0.06%)  0/1680 (0.00%) 
LIVER DISORDER  1  1/1678 (0.06%)  0/1680 (0.00%) 
Immune system disorders     
FOOD ALLERGY  1  1/1678 (0.06%)  0/1680 (0.00%) 
Infections and infestations     
ABSCESS JAW  1  1/1678 (0.06%)  0/1680 (0.00%) 
ABSCESS LIMB  1  0/1678 (0.00%)  1/1680 (0.06%) 
APPENDICITIS  1  1/1678 (0.06%)  1/1680 (0.06%) 
ATYPICAL MYCOBACTERIAL INFECTION  1  0/1678 (0.00%)  1/1680 (0.06%) 
BACTERAEMIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
BRONCHITIS  1  0/1678 (0.00%)  4/1680 (0.24%) 
CHOLECYSTITIS INFECTIVE  1  0/1678 (0.00%)  1/1680 (0.06%) 
CYSTITIS  1  1/1678 (0.06%)  1/1680 (0.06%) 
DEVICE RELATED INFECTION  1  2/1678 (0.12%)  0/1680 (0.00%) 
DIVERTICULITIS  1  1/1678 (0.06%)  1/1680 (0.06%) 
ECZEMA INFECTED  1  0/1678 (0.00%)  1/1680 (0.06%) 
ENTEROCOLITIS INFECTIOUS  1  0/1678 (0.00%)  1/1680 (0.06%) 
ERYSIPELAS  1  0/1678 (0.00%)  2/1680 (0.12%) 
GASTROENTERITIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
GASTROENTERITIS ROTAVIRUS  1  1/1678 (0.06%)  0/1680 (0.00%) 
H1N1 INFLUENZA  1  0/1678 (0.00%)  1/1680 (0.06%) 
HERPES ZOSTER  1  0/1678 (0.00%)  1/1680 (0.06%) 
INFECTED SKIN ULCER  1  1/1678 (0.06%)  0/1680 (0.00%) 
INFECTIOUS PLEURAL EFFUSION  1  2/1678 (0.12%)  0/1680 (0.00%) 
INFECTIVE ANEURYSM  1  1/1678 (0.06%)  0/1680 (0.00%) 
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE  1  1/1678 (0.06%)  1/1680 (0.06%) 
INFLUENZA  1  1/1678 (0.06%)  1/1680 (0.06%) 
LOWER RESPIRATORY TRACT INFECTION  1  8/1678 (0.48%)  7/1680 (0.42%) 
LOWER RESPIRATORY TRACT INFECTION BACTERIAL  1  1/1678 (0.06%)  0/1680 (0.00%) 
LOWER RESPIRATORY TRACT INFECTION VIRAL  1  1/1678 (0.06%)  0/1680 (0.00%) 
LUNG INFECTION  1  0/1678 (0.00%)  3/1680 (0.18%) 
MENINGITIS VIRAL  1  0/1678 (0.00%)  1/1680 (0.06%) 
NASOPHARYNGITIS  1  0/1678 (0.00%)  2/1680 (0.12%) 
ORAL VIRAL INFECTION  1  1/1678 (0.06%)  0/1680 (0.00%) 
OTITIS EXTERNA  1  1/1678 (0.06%)  0/1680 (0.00%) 
OTITIS MEDIA CHRONIC  1  1/1678 (0.06%)  0/1680 (0.00%) 
PERITONITIS  1  1/1678 (0.06%)  2/1680 (0.12%) 
PHARYNGITIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
PNEUMOCOCCAL INFECTION  1  0/1678 (0.00%)  1/1680 (0.06%) 
PNEUMONIA  1  34/1678 (2.03%)  54/1680 (3.21%) 
PNEUMONIA BACTERIAL  1  0/1678 (0.00%)  1/1680 (0.06%) 
PSEUDOMONAS INFECTION  1  0/1678 (0.00%)  1/1680 (0.06%) 
PULMONARY SEPSIS  1  4/1678 (0.24%)  1/1680 (0.06%) 
PULMONARY TUBERCULOSIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
PYELONEPHRITIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
RESPIRATORY TRACT INFECTION  1  2/1678 (0.12%)  1/1680 (0.06%) 
RESPIRATORY TRACT INFECTION BACTERIAL  1  1/1678 (0.06%)  0/1680 (0.00%) 
SEPSIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
SEPTIC SHOCK  1  1/1678 (0.06%)  1/1680 (0.06%) 
SINUSITIS  1  2/1678 (0.12%)  1/1680 (0.06%) 
SPUTUM PURULENT  1  0/1678 (0.00%)  1/1680 (0.06%) 
TUBERCULOUS PLEURISY  1  1/1678 (0.06%)  0/1680 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION  1  2/1678 (0.12%)  1/1680 (0.06%) 
UPPER RESPIRATORY TRACT INFECTION BACTERIAL  1  9/1678 (0.54%)  15/1680 (0.89%) 
URETERITIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
URINARY TRACT INFECTION  1  1/1678 (0.06%)  0/1680 (0.00%) 
UROSEPSIS  1  1/1678 (0.06%)  1/1680 (0.06%) 
VIRAL INFECTION  1  1/1678 (0.06%)  0/1680 (0.00%) 
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  1/1678 (0.06%)  2/1680 (0.12%) 
Injury, poisoning and procedural complications     
ANAEMIA POSTOPERATIVE  1  0/1678 (0.00%)  1/1680 (0.06%) 
ANKLE FRACTURE  1  1/1678 (0.06%)  1/1680 (0.06%) 
BRAIN HERNIATION  1  0/1678 (0.00%)  1/1680 (0.06%) 
CARBON MONOXIDE POISONING  1  0/1678 (0.00%)  1/1680 (0.06%) 
CLAVICLE FRACTURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
COMPRESSION FRACTURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
FALL  1  0/1678 (0.00%)  1/1680 (0.06%) 
FEMORAL NECK FRACTURE  1  1/1678 (0.06%)  1/1680 (0.06%) 
FEMUR FRACTURE  1  1/1678 (0.06%)  1/1680 (0.06%) 
HEAD INJURY  1  1/1678 (0.06%)  0/1680 (0.00%) 
HIP FRACTURE  1  2/1678 (0.12%)  1/1680 (0.06%) 
HUMERUS FRACTURE  1  1/1678 (0.06%)  1/1680 (0.06%) 
LIMB INJURY  1  0/1678 (0.00%)  1/1680 (0.06%) 
MENISCUS INJURY  1  0/1678 (0.00%)  2/1680 (0.12%) 
OVERDOSE  1  2/1678 (0.12%)  1/1680 (0.06%) 
PATELLA FRACTURE  1  1/1678 (0.06%)  0/1680 (0.00%) 
PELVIC FRACTURE  1  1/1678 (0.06%)  0/1680 (0.00%) 
POSTOPERATIVE WOUND COMPLICATION  1  1/1678 (0.06%)  0/1680 (0.00%) 
PROCEDURAL INTESTINAL PERFORATION  1  0/1678 (0.00%)  1/1680 (0.06%) 
RIB FRACTURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
SPINAL COMPRESSION FRACTURE  1  1/1678 (0.06%)  0/1680 (0.00%) 
SPINAL FRACTURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
TIBIA FRACTURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
WOUND DECOMPOSITION  1  1/1678 (0.06%)  0/1680 (0.00%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  0/1678 (0.00%)  1/1680 (0.06%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  1/1678 (0.06%)  2/1680 (0.12%) 
BLOOD POTASSIUM INCREASED  1  1/1678 (0.06%)  0/1680 (0.00%) 
WEIGHT DECREASED  1  0/1678 (0.00%)  1/1680 (0.06%) 
Metabolism and nutrition disorders     
ACIDOSIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
CACHEXIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
DEHYDRATION  1  1/1678 (0.06%)  0/1680 (0.00%) 
DIABETES MELLITUS  1  1/1678 (0.06%)  3/1680 (0.18%) 
DIET REFUSAL  1  1/1678 (0.06%)  0/1680 (0.00%) 
ELECTROLYTE IMBALANCE  1  1/1678 (0.06%)  0/1680 (0.00%) 
HYPERGLYCAEMIA  1  1/1678 (0.06%)  1/1680 (0.06%) 
HYPERKALAEMIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
HYPONATRAEMIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
ARTHROPATHY  1  1/1678 (0.06%)  0/1680 (0.00%) 
GROIN PAIN  1  1/1678 (0.06%)  0/1680 (0.00%) 
INTERVERTEBRAL DISC PROTRUSION  1  0/1678 (0.00%)  1/1680 (0.06%) 
MUSCLE HAEMORRHAGE  1  1/1678 (0.06%)  0/1680 (0.00%) 
OSTEOARTHRITIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
OSTEOLYSIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
OSTEOPOROTIC FRACTURE  1  1/1678 (0.06%)  0/1680 (0.00%) 
POLYMYALGIA RHEUMATICA  1  2/1678 (0.12%)  0/1680 (0.00%) 
SPINAL PAIN  1  0/1678 (0.00%)  1/1680 (0.06%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
ACUTE MYELOID LEUKAEMIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
ADENOCARCINOMA GASTRIC  1  0/1678 (0.00%)  1/1680 (0.06%) 
ADENOCARCINOMA OF COLON  1  1/1678 (0.06%)  1/1680 (0.06%) 
ADRENAL GLAND CANCER  1  0/1678 (0.00%)  1/1680 (0.06%) 
B-CELL LYMPHOMA  1  0/1678 (0.00%)  1/1680 (0.06%) 
BASAL CELL CARCINOMA  1  2/1678 (0.12%)  0/1680 (0.00%) 
BREAST CANCER  1  0/1678 (0.00%)  1/1680 (0.06%) 
BRONCHIAL CARCINOMA  1  1/1678 (0.06%)  1/1680 (0.06%) 
CHRONIC MYELOID LEUKAEMIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
COLON CANCER  1  1/1678 (0.06%)  2/1680 (0.12%) 
DIFFUSE LARGE B-CELL LYMPHOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
GASTRIC CANCER  1  1/1678 (0.06%)  0/1680 (0.00%) 
HEPATIC CANCER  1  1/1678 (0.06%)  0/1680 (0.00%) 
HYPOPHARYNGEAL CANCER  1  0/1678 (0.00%)  1/1680 (0.06%) 
LARGE INTESTINE BENIGN NEOPLASM  1  1/1678 (0.06%)  0/1680 (0.00%) 
LARYNGEAL CANCER  1  1/1678 (0.06%)  1/1680 (0.06%) 
LARYNGEAL SQUAMOUS CELL CARCINOMA  1  0/1678 (0.00%)  1/1680 (0.06%) 
LUNG ADENOCARCINOMA METASTATIC  1  1/1678 (0.06%)  0/1680 (0.00%) 
LUNG NEOPLASM MALIGNANT  1  3/1678 (0.18%)  6/1680 (0.36%) 
MALIGNANT MESENCHYMOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
METASTASES TO LIVER  1  1/1678 (0.06%)  0/1680 (0.00%) 
MYELOID LEUKAEMIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
NEOPLASM MALIGNANT  1  1/1678 (0.06%)  0/1680 (0.00%) 
NON-HODGKIN'S LYMPHOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
NON-SMALL CELL LUNG CANCER  1  1/1678 (0.06%)  0/1680 (0.00%) 
OESOPHAGEAL CARCINOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
PENILE NEOPLASM  1  0/1678 (0.00%)  1/1680 (0.06%) 
PLASMA CELL MYELOMA  1  0/1678 (0.00%)  1/1680 (0.06%) 
PROSTATE CANCER  1  4/1678 (0.24%)  2/1680 (0.12%) 
RECTAL ADENOCARCINOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
RECTAL CANCER  1  1/1678 (0.06%)  1/1680 (0.06%) 
RENAL CANCER  1  0/1678 (0.00%)  1/1680 (0.06%) 
SMALL CELL CARCINOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
SMALL CELL LUNG CANCER  1  1/1678 (0.06%)  0/1680 (0.00%) 
SQUAMOUS CELL CARCINOMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
SQUAMOUS CELL CARCINOMA OF LUNG  1  1/1678 (0.06%)  1/1680 (0.06%) 
TONGUE NEOPLASM MALIGNANT STAGE UNSPECIFIED  1  1/1678 (0.06%)  0/1680 (0.00%) 
URETHRAL CANCER  1  1/1678 (0.06%)  0/1680 (0.00%) 
Nervous system disorders     
BASAL GANGLIA STROKE  1  0/1678 (0.00%)  1/1680 (0.06%) 
BRAIN INJURY  1  1/1678 (0.06%)  0/1680 (0.00%) 
BRAIN STEM HAEMORRHAGE  1  0/1678 (0.00%)  1/1680 (0.06%) 
CAROTID ARTERIOSCLEROSIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
CAROTID ARTERY OCCLUSION  1  0/1678 (0.00%)  1/1680 (0.06%) 
CENTRAL NERVOUS SYSTEM LESION  1  0/1678 (0.00%)  1/1680 (0.06%) 
CEREBELLAR INFARCTION  1  0/1678 (0.00%)  1/1680 (0.06%) 
CEREBRAL INFARCTION  1  2/1678 (0.12%)  0/1680 (0.00%) 
CEREBRAL ISCHAEMIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
CEREBRAL THROMBOSIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
CEREBROVASCULAR ACCIDENT  1  0/1678 (0.00%)  2/1680 (0.12%) 
CLUSTER HEADACHE  1  0/1678 (0.00%)  1/1680 (0.06%) 
DEPRESSED LEVEL OF CONSCIOUSNESS  1  1/1678 (0.06%)  0/1680 (0.00%) 
DIZZINESS  1  1/1678 (0.06%)  1/1680 (0.06%) 
EPILEPSY  1  1/1678 (0.06%)  0/1680 (0.00%) 
HEADACHE  1  0/1678 (0.00%)  1/1680 (0.06%) 
HEMIPARESIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
HYDROCEPHALUS  1  0/1678 (0.00%)  1/1680 (0.06%) 
ISCHAEMIC STROKE  1  2/1678 (0.12%)  0/1680 (0.00%) 
LACUNAR INFARCTION  1  0/1678 (0.00%)  1/1680 (0.06%) 
SYNCOPE  1  2/1678 (0.12%)  0/1680 (0.00%) 
TRANSIENT ISCHAEMIC ATTACK  1  1/1678 (0.06%)  1/1680 (0.06%) 
VIITH NERVE PARALYSIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
Psychiatric disorders     
ANXIETY  1  1/1678 (0.06%)  0/1680 (0.00%) 
COMPLETED SUICIDE  1  0/1678 (0.00%)  1/1680 (0.06%) 
DELIRIUM TREMENS  1  1/1678 (0.06%)  0/1680 (0.00%) 
DEPRESSION  1  1/1678 (0.06%)  0/1680 (0.00%) 
HALLUCINATION  1  1/1678 (0.06%)  0/1680 (0.00%) 
SLEEP DISORDER  1  0/1678 (0.00%)  1/1680 (0.06%) 
Renal and urinary disorders     
ACUTE KIDNEY INJURY  1  1/1678 (0.06%)  0/1680 (0.00%) 
CALCULUS URINARY  1  0/1678 (0.00%)  1/1680 (0.06%) 
CHRONIC KIDNEY DISEASE  1  0/1678 (0.00%)  1/1680 (0.06%) 
NEPHROLITHIASIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
RENAL FAILURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
URETHRAL STENOSIS  1  2/1678 (0.12%)  0/1680 (0.00%) 
URINARY RETENTION  1  1/1678 (0.06%)  1/1680 (0.06%) 
Reproductive system and breast disorders     
BENIGN PROSTATIC HYPERPLASIA  1  0/1678 (0.00%)  2/1680 (0.12%) 
TESTICULAR TORSION  1  1/1678 (0.06%)  0/1680 (0.00%) 
UTERINE POLYP  1  0/1678 (0.00%)  1/1680 (0.06%) 
Respiratory, thoracic and mediastinal disorders     
ACUTE PULMONARY OEDEMA  1  0/1678 (0.00%)  1/1680 (0.06%) 
ACUTE RESPIRATORY FAILURE  1  5/1678 (0.30%)  4/1680 (0.24%) 
ASTHMA  1  0/1678 (0.00%)  1/1680 (0.06%) 
BRONCHITIS CHRONIC  1  0/1678 (0.00%)  1/1680 (0.06%) 
BRONCHOPLEURAL FISTULA  1  0/1678 (0.00%)  1/1680 (0.06%) 
BRONCHOSPASM  1  1/1678 (0.06%)  0/1680 (0.00%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  182/1678 (10.85%)  207/1680 (12.32%) 
CHRONIC RESPIRATORY FAILURE  1  4/1678 (0.24%)  1/1680 (0.06%) 
COUGH  1  0/1678 (0.00%)  2/1680 (0.12%) 
DYSPNOEA  1  8/1678 (0.48%)  4/1680 (0.24%) 
EMPHYSEMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
EPISTAXIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
HAEMOPTYSIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
HAEMOTHORAX  1  0/1678 (0.00%)  1/1680 (0.06%) 
HYPERCAPNIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
HYPOXIA  1  0/1678 (0.00%)  1/1680 (0.06%) 
LARYNGEAL OEDEMA  1  1/1678 (0.06%)  0/1680 (0.00%) 
LUNG CONSOLIDATION  1  1/1678 (0.06%)  0/1680 (0.00%) 
PLEURAL EFFUSION  1  0/1678 (0.00%)  1/1680 (0.06%) 
PLEURISY  1  2/1678 (0.12%)  1/1680 (0.06%) 
PNEUMONITIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
PNEUMOTHORAX  1  2/1678 (0.12%)  5/1680 (0.30%) 
PNEUMOTHORAX SPONTANEOUS  1  0/1678 (0.00%)  1/1680 (0.06%) 
PULMONARY EMBOLISM  1  4/1678 (0.24%)  2/1680 (0.12%) 
PULMONARY HAEMORRHAGE  1  0/1678 (0.00%)  1/1680 (0.06%) 
PULMONARY HILAR ENLARGEMENT  1  0/1678 (0.00%)  1/1680 (0.06%) 
PULMONARY HYPERTENSION  1  1/1678 (0.06%)  0/1680 (0.00%) 
PULMONARY OEDEMA  1  0/1678 (0.00%)  1/1680 (0.06%) 
RESPIRATORY ACIDOSIS  1  2/1678 (0.12%)  0/1680 (0.00%) 
RESPIRATORY FAILURE  1  11/1678 (0.66%)  6/1680 (0.36%) 
Skin and subcutaneous tissue disorders     
LINEAR IGA DISEASE  1  0/1678 (0.00%)  1/1680 (0.06%) 
PARAPSORIASIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
SWELLING FACE  1  0/1678 (0.00%)  1/1680 (0.06%) 
URTICARIA  1  1/1678 (0.06%)  0/1680 (0.00%) 
Vascular disorders     
AORTIC ANEURYSM  1  2/1678 (0.12%)  3/1680 (0.18%) 
AORTIC ANEURYSM RUPTURE  1  0/1678 (0.00%)  1/1680 (0.06%) 
AORTIC CALCIFICATION  1  0/1678 (0.00%)  1/1680 (0.06%) 
ARTERIOSCLEROSIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
CIRCULATORY COLLAPSE  1  1/1678 (0.06%)  0/1680 (0.00%) 
DEEP VEIN THROMBOSIS  1  2/1678 (0.12%)  0/1680 (0.00%) 
EMBOLISM ARTERIAL  1  0/1678 (0.00%)  1/1680 (0.06%) 
HYPERTENSION  1  3/1678 (0.18%)  2/1680 (0.12%) 
HYPERTENSIVE CRISIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
HYPOTENSION  1  2/1678 (0.12%)  0/1680 (0.00%) 
LERICHE SYNDROME  1  1/1678 (0.06%)  0/1680 (0.00%) 
ORTHOSTATIC HYPOTENSION  1  1/1678 (0.06%)  0/1680 (0.00%) 
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE  1  4/1678 (0.24%)  0/1680 (0.00%) 
PERIPHERAL EMBOLISM  1  0/1678 (0.00%)  1/1680 (0.06%) 
TEMPORAL ARTERITIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
THROMBOPHLEBITIS  1  1/1678 (0.06%)  0/1680 (0.00%) 
THROMBOSIS  1  0/1678 (0.00%)  1/1680 (0.06%) 
VARICOSE ULCERATION  1  0/1678 (0.00%)  1/1680 (0.06%) 
VENOUS THROMBOSIS  1  1/1678 (0.06%)  0/1680 (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 Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Affected / at Risk (%) Affected / at Risk (%)
Total   1363/1678 (81.23%)   1424/1680 (84.76%) 
Gastrointestinal disorders     
CONSTIPATION  1  19/1678 (1.13%)  17/1680 (1.01%) 
DIARRHOEA  1  19/1678 (1.13%)  24/1680 (1.43%) 
DYSPEPSIA  1  18/1678 (1.07%)  9/1680 (0.54%) 
GASTRITIS  1  10/1678 (0.60%)  20/1680 (1.19%) 
General disorders     
NON-CARDIAC CHEST PAIN  1  20/1678 (1.19%)  11/1680 (0.65%) 
OEDEMA PERIPHERAL  1  26/1678 (1.55%)  13/1680 (0.77%) 
PYREXIA  1  17/1678 (1.01%)  27/1680 (1.61%) 
Infections and infestations     
BRONCHITIS  1  29/1678 (1.73%)  41/1680 (2.44%) 
GASTROENTERITIS  1  10/1678 (0.60%)  18/1680 (1.07%) 
INFLUENZA  1  34/1678 (2.03%)  55/1680 (3.27%) 
LOWER RESPIRATORY TRACT INFECTION  1  76/1678 (4.53%)  91/1680 (5.42%) 
NASOPHARYNGITIS  1  197/1678 (11.74%)  194/1680 (11.55%) 
ORAL CANDIDIASIS  1  20/1678 (1.19%)  71/1680 (4.23%) 
OROPHARYNGEAL CANDIDIASIS  1  2/1678 (0.12%)  17/1680 (1.01%) 
PNEUMONIA  1  19/1678 (1.13%)  27/1680 (1.61%) 
RESPIRATORY TRACT INFECTION VIRAL  1  17/1678 (1.01%)  8/1680 (0.48%) 
RHINITIS  1  27/1678 (1.61%)  28/1680 (1.67%) 
SINUSITIS  1  16/1678 (0.95%)  20/1680 (1.19%) 
UPPER RESPIRATORY TRACT INFECTION  1  79/1678 (4.71%)  82/1680 (4.88%) 
UPPER RESPIRATORY TRACT INFECTION BACTERIAL  1  121/1678 (7.21%)  157/1680 (9.35%) 
URINARY TRACT INFECTION  1  14/1678 (0.83%)  22/1680 (1.31%) 
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  131/1678 (7.81%)  136/1680 (8.10%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  20/1678 (1.19%)  23/1680 (1.37%) 
BACK PAIN  1  35/1678 (2.09%)  34/1680 (2.02%) 
MUSCULOSKELETAL PAIN  1  17/1678 (1.01%)  13/1680 (0.77%) 
Nervous system disorders     
DIZZINESS  1  6/1678 (0.36%)  27/1680 (1.61%) 
HEADACHE  1  38/1678 (2.26%)  34/1680 (2.02%) 
Respiratory, thoracic and mediastinal disorders     
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  1262/1678 (75.21%)  1331/1680 (79.23%) 
COUGH  1  50/1678 (2.98%)  49/1680 (2.92%) 
DYSPHONIA  1  7/1678 (0.42%)  30/1680 (1.79%) 
DYSPNOEA  1  41/1678 (2.44%)  47/1680 (2.80%) 
OROPHARYNGEAL PAIN  1  35/1678 (2.09%)  33/1680 (1.96%) 
SPUTUM INCREASED  1  10/1678 (0.60%)  23/1680 (1.37%) 
Vascular disorders     
HYPERTENSION  1  44/1678 (2.62%)  40/1680 (2.38%) 
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
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01782326     History of Changes
Other Study ID Numbers: CQVA149A2318
First Submitted: January 30, 2013
First Posted: February 1, 2013
Results First Submitted: May 4, 2016
Results First Posted: May 16, 2016
Last Update Posted: May 16, 2016