Trial Outcomes & Findings for QVA vs. Salmeterol/Fluticasone, 52-week Exacerbation Study, FLAME (EFfect of Indacaterol Glycopyronium Vs Fluticasone Salmeterol on COPD Exacerbations) (NCT NCT01782326)
NCT ID: NCT01782326
Last Updated: 2016-05-16
Results Overview
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.
COMPLETED
PHASE3
3362 participants
52 weeks
2016-05-16
Participant Flow
Participant milestones
| Measure |
QVA149
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Planned Treatment Epoch
STARTED
|
1680
|
1682
|
|
Planned Treatment Epoch
Full Analysis Set (FAS)
|
1675
|
1679
|
|
Planned Treatment Epoch
Per-protocol Set (PPS)
|
1528
|
1556
|
|
Planned Treatment Epoch
Serial Spirometry Set
|
280
|
279
|
|
Planned Treatment Epoch
Safety Set (SAF)
|
1678
|
1680
|
|
Planned Treatment Epoch
Urine Cortisol Set
|
266
|
269
|
|
Planned Treatment Epoch
COMPLETED
|
1478
|
1474
|
|
Planned Treatment Epoch
NOT COMPLETED
|
202
|
208
|
|
Double-blind Treatment
STARTED
|
1678
|
1680
|
|
Double-blind Treatment
COMPLETED
|
1400
|
1360
|
|
Double-blind Treatment
NOT COMPLETED
|
278
|
320
|
Reasons for withdrawal
| Measure |
QVA149
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Planned Treatment Epoch
Subject/guardian decision
|
149
|
151
|
|
Planned Treatment Epoch
Death
|
29
|
30
|
|
Planned Treatment Epoch
Physician Decision
|
18
|
16
|
|
Planned Treatment Epoch
Protocol deviation
|
2
|
3
|
|
Planned Treatment Epoch
Lost to Follow-up
|
4
|
4
|
|
Planned Treatment Epoch
Technical problems
|
0
|
4
|
|
Double-blind Treatment
Adverse Event
|
129
|
145
|
|
Double-blind Treatment
Subject/guardian decision
|
111
|
125
|
|
Double-blind Treatment
Lack of Efficacy
|
17
|
22
|
|
Double-blind Treatment
Physician Decision
|
13
|
16
|
|
Double-blind Treatment
Protocol deviation
|
8
|
7
|
|
Double-blind Treatment
Technical problems
|
0
|
5
|
Baseline Characteristics
QVA vs. Salmeterol/Fluticasone, 52-week Exacerbation Study, FLAME (EFfect of Indacaterol Glycopyronium Vs Fluticasone Salmeterol on COPD Exacerbations)
Baseline characteristics by cohort
| Measure |
QVA149
n=1680 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1682 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
Total
n=3362 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.6 Years
STANDARD_DEVIATION 7.89 • n=5 Participants
|
64.5 Years
STANDARD_DEVIATION 7.70 • n=7 Participants
|
64.6 Years
STANDARD_DEVIATION 7.79 • n=5 Participants
|
|
Sex: Female, Male
Female
|
381 Participants
n=5 Participants
|
424 Participants
n=7 Participants
|
805 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1299 Participants
n=5 Participants
|
1258 Participants
n=7 Participants
|
2557 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1528 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1556 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Rate of COPD Exacerbations
|
3.59 COPD Exacerbations/year
Interval 3.28 to 3.94
|
4.03 COPD Exacerbations/year
Interval 3.68 to 4.41
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Time to First COPD Exacerbation.
|
71.0 Days
Interval 60.0 to 82.0
|
51.0 Days
Interval 46.0 to 57.0
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1651 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1656 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Rate of Moderate to Severe COPD Exacerbations.
|
0.98 COPD Exacerbation/year
Interval 0.88 to 1.1
|
1.19 COPD Exacerbation/year
Interval 1.07 to 1.32
|
SECONDARY outcome
Timeframe: 52 weeks.Population: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Time to First Moderate to Severe COPD Exacerbation.
|
NA Days
NA -Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
|
308.0 Days
Interval 283.0 to 352.0
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1651 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1656 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids
|
0.18 COPD Exacerbation/year
Interval 0.14 to 0.22
|
0.18 COPD Exacerbation/year
Interval 0.14 to 0.23
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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 .
Outcome measures
| Measure |
QVA149
n=1651 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1656 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics
|
0.17 COPD Exacerbation/year
Interval 0.13 to 0.22
|
0.22 COPD Exacerbation/year
Interval 0.17 to 0.28
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1651 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1656 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Rate of Moderate to Severe COPD Exacerbations Requiring Hospitalization. COPD Exacerbations Starting Between First Dose and One Day After Last Treatment Are Included.
|
0.15 COPD Exacerbation/year
Interval 0.11 to 0.19
|
0.17 COPD Exacerbation/year
Interval 0.13 to 0.22
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Rate of Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days
|
0.0 COPD Exacerbation/year
Standard Deviation 0.15
|
0.0 COPD Exacerbation/year
Standard Deviation 0.12
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids
|
NA Days
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
|
NA Days
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics
|
NA Days
NA- Parameters not estimated, data did not reach median
|
NA Days
NA- Parameters not estimated, data did not reach median
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Time to First Moderate to Severe COPD Exacerbations Requiring Hospitalization
|
NA Days
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
|
NA Days
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Time to First Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days
|
NA Days
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
|
NA Days
NA- Parameters not estimated since less than 50% of the patients had an event, the median could not be calculated
|
SECONDARY outcome
Timeframe: Baseline, day 1 (30 min and one hour post dose)Population: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second
Day 1, 30 min post-dose (n=1659, 1663)
|
0.121 Liters
Standard Error 0.0049
|
0.076 Liters
Standard Error 0.0049
|
|
Forced Expiratory Volume in 1 Second
Day 1, one hour post-dose (n=1657, 1664)
|
0.147 Liters
Standard Error 0.0054
|
0.092 Liters
Standard Error 0.0054
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1597 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1595 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second
|
0.079 Liters
Standard Error 0.0070
|
0.006 Liters
Standard Error 0.0070
|
SECONDARY outcome
Timeframe: Baseline, 12 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1597 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1595 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second
|
0.070 Liters
Standard Error 0.0072
|
-0.008 Liters
Standard Error 0.0072
|
SECONDARY outcome
Timeframe: Baseline, 26 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1597 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1595 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second
|
0.049 Liters
Standard Error 0.0073
|
-0.037 Liters
Standard Error 0.0074
|
SECONDARY outcome
Timeframe: Baseline, 38 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1597 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1595 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second
|
0.034 Liters
Standard Error 0.0074
|
-0.039 Liters
Standard Error 0.0075
|
SECONDARY outcome
Timeframe: Baseline, 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1597 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1595 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second
|
0.015 Liters
Standard Error 0.0075
|
-0.048 Liters
Standard Error 0.0076
|
SECONDARY outcome
Timeframe: Baseline, 52 weeksPopulation: 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.
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"
Outcome measures
| Measure |
QVA149
n=279 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=277 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in 1 Second AUC (0-12h)
|
0.078 Liters
Standard Error 0.0174
|
-0.032 Liters
Standard Error 0.0176
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1602 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1593 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in Total St. George's Respiratory Questionnaire Score
|
-2.3 Score on a scale
Standard Error 0.36
|
-2.3 Score on a scale
Standard Error 0.36
|
SECONDARY outcome
Timeframe: Baseline, 12 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1602 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1593 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in Total St. George's Respiratory Questionnaire Score
|
-3.2 Score on a scale
Standard Error 0.38
|
-1.9 Score on a scale
Standard Error 0.38
|
SECONDARY outcome
Timeframe: Baseline, 26 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1602 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1593 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in Total St. George's Respiratory Questionnaire Score
|
-3.5 Score on a scale
Standard Error 0.39
|
-2.3 Score on a scale
Standard Error 0.39
|
SECONDARY outcome
Timeframe: Baseline, 38 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1602 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1593 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in Total St. George's Respiratory Questionnaire Score
|
-3.5 Score on a scale
Standard Error 0.40
|
-1.7 Score on a scale
Standard Error 0.40
|
SECONDARY outcome
Timeframe: Baseline, 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1602 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1593 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in Total St. George's Respiratory Questionnaire Score
|
-3.1 Score on a scale
Standard Error 0.41
|
-1.9 Score on a scale
Standard Error 0.41
|
SECONDARY outcome
Timeframe: Baseline, 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
QVA149
n=1675 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1679 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in the Number of Puffs of Rescue Medication
|
-1.01 Number of puffs per day
Standard Error 0.097
|
-0.76 Number of puffs per day
Standard Error 0.097
|
SECONDARY outcome
Timeframe: Baseline, 52 WeeksPopulation: 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.
Urine cortisol/creatinine ratio
Outcome measures
| Measure |
QVA149
n=162 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=154 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
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.
|
5.615 ng/mL
Full Range 26.633 • Interval -96.93 to 509.17
|
-10.390 ng/mL
Full Range 54.428 • Interval -97.76 to 4444.65
|
SECONDARY outcome
Timeframe: 4 Weeks, 12 Weeks, 26 Weeks, 38 Weeks, 52 WeeksPopulation: 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
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
Outcome measures
| Measure |
QVA149
n=1597 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1595 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Change From Baseline in Forced Vital Capacity
4 weeks
|
0.146 Liters
Standard Error 0.0127
|
-0.032 Liters
Standard Error 0.0128
|
|
Change From Baseline in Forced Vital Capacity
12 weeks
|
0.134 Liters
Standard Error 0.0131
|
-0.071 Liters
Standard Error 0.0131
|
|
Change From Baseline in Forced Vital Capacity
26 weeks
|
0.088 Liters
Standard Error 0.0135
|
-0.121 Liters
Standard Error 0.0136
|
|
Change From Baseline in Forced Vital Capacity
38 weeks
|
0.071 Liters
Standard Error 0.0137
|
-0.111 Liters
Standard Error 0.0137
|
|
Change From Baseline in Forced Vital Capacity
52 weeks
|
0.022 Liters
Standard Error 0.0139
|
-0.138 Liters
Standard Error 0.0140
|
SECONDARY outcome
Timeframe: 52 weeks of treatment + 30 daysPopulation: 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
The overall rate of adverse events reported from initiation through 30 days post last dose.
Outcome measures
| Measure |
QVA149
n=1678 Participants
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1680 Participants
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Number of Patients With Adverse Events, Serious Adverse Events, and Death
Patients with at least one SAEs
|
308 Number of participants
|
334 Number of participants
|
|
Number of Patients With Adverse Events, Serious Adverse Events, and Death
Patients with at least one AE
|
1459 Number of participants
|
1498 Number of participants
|
|
Number of Patients With Adverse Events, Serious Adverse Events, and Death
Death
|
24 Number of participants
|
24 Number of participants
|
Adverse Events
QVA149
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
Serious adverse events
| Measure |
QVA149
n=1678 participants at risk
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1680 participants at risk
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Cardiac disorders
SINUS TACHYCARDIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
PULMONARY TUBERCULOSIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
VENTRICULAR ARRHYTHMIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Congenital, familial and genetic disorders
PROGRESSIVE CEREBELLAR DEGENERATION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.48%
8/1678
|
0.24%
4/1680
|
|
Respiratory, thoracic and mediastinal disorders
EMPHYSEMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Blood and lymphatic system disorders
HEPARIN-INDUCED THROMBOCYTOPENIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Blood and lymphatic system disorders
HYPOCHROMIC ANAEMIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
ACUTE CORONARY SYNDROME
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.24%
4/1678
|
0.12%
2/1680
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
ARRHYTHMIA
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.30%
5/1678
|
0.42%
7/1680
|
|
Cardiac disorders
ATRIAL FLUTTER
|
0.12%
2/1678
|
0.18%
3/1680
|
|
Cardiac disorders
ATRIAL TACHYCARDIA
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Cardiac disorders
BRADYCARDIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Cardiac disorders
CARDIAC ARREST
|
0.30%
5/1678
|
0.06%
1/1680
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.30%
5/1678
|
0.42%
7/1680
|
|
Cardiac disorders
CARDIAC FAILURE ACUTE
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.06%
1/1678
|
0.18%
3/1680
|
|
Cardiac disorders
CARDIAC TAMPONADE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.06%
1/1678
|
0.18%
3/1680
|
|
Cardiac disorders
CARDIOVASCULAR DISORDER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Cardiac disorders
CONGESTIVE CARDIOMYOPATHY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Cardiac disorders
COR PULMONALE
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Cardiac disorders
COR PULMONALE CHRONIC
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.12%
2/1678
|
0.06%
1/1680
|
|
Cardiac disorders
CORONARY ARTERY STENOSIS
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Cardiac disorders
ISCHAEMIC CARDIOMYOPATHY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Cardiac disorders
LEFT VENTRICULAR DYSFUNCTION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
LEFT VENTRICULAR FAILURE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.36%
6/1678
|
0.30%
5/1680
|
|
Cardiac disorders
MYOCARDIAL ISCHAEMIA
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Cardiac disorders
MYOCARDIAL RUPTURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Cardiac disorders
PERICARDIAL HAEMORRHAGE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Cardiac disorders
RIGHT VENTRICULAR FAILURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Endocrine disorders
GOITRE
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Eye disorders
ANGLE CLOSURE GLAUCOMA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Eye disorders
OPHTHALMOPLEGIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Eye disorders
OPTIC ISCHAEMIC NEUROPATHY
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Eye disorders
RETINAL DETACHMENT
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
ABDOMINAL HERNIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
ACID PEPTIC DISEASE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
ASCITES
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
COLITIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
DUODENAL ULCER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
FAECALOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
GASTRIC ULCER
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
GASTRITIS
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
0.00%
0/1678
|
0.18%
3/1680
|
|
Gastrointestinal disorders
HAEMATEMESIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
ILEUS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
ILEUS PARALYTIC
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
INTESTINAL PERFORATION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
INTESTINAL STENOSIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
LARGE INTESTINE POLYP
|
0.00%
0/1678
|
0.24%
4/1680
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
OESOPHAGITIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Gastrointestinal disorders
PANCREATITIS ACUTE
|
0.06%
1/1678
|
0.18%
3/1680
|
|
Gastrointestinal disorders
STOMATITIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
UMBILICAL HERNIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/1678
|
0.06%
1/1680
|
|
General disorders
ASTHENIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
General disorders
FATIGUE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
General disorders
LOCAL SWELLING
|
0.06%
1/1678
|
0.00%
0/1680
|
|
General disorders
MULTI-ORGAN FAILURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.06%
1/1678
|
0.12%
2/1680
|
|
General disorders
OEDEMA PERIPHERAL
|
0.06%
1/1678
|
0.06%
1/1680
|
|
General disorders
PYREXIA
|
0.06%
1/1678
|
0.12%
2/1680
|
|
General disorders
SUDDEN CARDIAC DEATH
|
0.06%
1/1678
|
0.06%
1/1680
|
|
General disorders
SUDDEN DEATH
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Hepatobiliary disorders
DRUG-INDUCED LIVER INJURY
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
HEAD INJURY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Hepatobiliary disorders
HEPATIC CIRRHOSIS
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Hepatobiliary disorders
HEPATIC CYST RUPTURED
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Hepatobiliary disorders
LIVER DISORDER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Immune system disorders
FOOD ALLERGY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
ABSCESS JAW
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
ABSCESS LIMB
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
PYELONEPHRITIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
APPENDICITIS
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Infections and infestations
ATYPICAL MYCOBACTERIAL INFECTION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
BACTERAEMIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
BRONCHITIS
|
0.00%
0/1678
|
0.24%
4/1680
|
|
Infections and infestations
CHOLECYSTITIS INFECTIVE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
CYSTITIS
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Infections and infestations
DEVICE RELATED INFECTION
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Infections and infestations
DIVERTICULITIS
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Infections and infestations
ECZEMA INFECTED
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
ENTEROCOLITIS INFECTIOUS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
ERYSIPELAS
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
GASTROENTERITIS ROTAVIRUS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
H1N1 INFLUENZA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
HERPES ZOSTER
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
INFECTED SKIN ULCER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
INFECTIOUS PLEURAL EFFUSION
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Infections and infestations
INFECTIVE ANEURYSM
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Infections and infestations
INFLUENZA
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.48%
8/1678
|
0.42%
7/1680
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION BACTERIAL
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION VIRAL
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
LUNG INFECTION
|
0.00%
0/1678
|
0.18%
3/1680
|
|
Infections and infestations
RESPIRATORY TRACT INFECTION
|
0.12%
2/1678
|
0.06%
1/1680
|
|
Infections and infestations
MENINGITIS VIRAL
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
NASOPHARYNGITIS
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Infections and infestations
ORAL VIRAL INFECTION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
OTITIS EXTERNA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
OTITIS MEDIA CHRONIC
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
PERITONITIS
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Infections and infestations
PHARYNGITIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
PNEUMOCOCCAL INFECTION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
PNEUMONIA
|
2.0%
34/1678
|
3.2%
54/1680
|
|
Infections and infestations
PNEUMONIA BACTERIAL
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
PSEUDOMONAS INFECTION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
PULMONARY SEPSIS
|
0.24%
4/1678
|
0.06%
1/1680
|
|
Infections and infestations
RESPIRATORY TRACT INFECTION BACTERIAL
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
SEPSIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
SEPTIC SHOCK
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Infections and infestations
SINUSITIS
|
0.12%
2/1678
|
0.06%
1/1680
|
|
Infections and infestations
SPUTUM PURULENT
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
TUBERCULOUS PLEURISY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.12%
2/1678
|
0.06%
1/1680
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
0.54%
9/1678
|
0.89%
15/1680
|
|
Infections and infestations
URETERITIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
UROSEPSIS
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Infections and infestations
VIRAL INFECTION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Injury, poisoning and procedural complications
ANAEMIA POSTOPERATIVE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
ANKLE FRACTURE
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
BRAIN HERNIATION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
CARBON MONOXIDE POISONING
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
CLAVICLE FRACTURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
COMPRESSION FRACTURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
FEMUR FRACTURE
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.12%
2/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
HUMERUS FRACTURE
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
LIMB INJURY
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
MENISCUS INJURY
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Injury, poisoning and procedural complications
OVERDOSE
|
0.12%
2/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
PATELLA FRACTURE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Injury, poisoning and procedural complications
PELVIC FRACTURE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Injury, poisoning and procedural complications
POSTOPERATIVE WOUND COMPLICATION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Injury, poisoning and procedural complications
PROCEDURAL INTESTINAL PERFORATION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
RIB FRACTURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
SPINAL COMPRESSION FRACTURE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Injury, poisoning and procedural complications
SPINAL FRACTURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
TIBIA FRACTURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Injury, poisoning and procedural complications
WOUND DECOMPOSITION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Investigations
BLOOD POTASSIUM INCREASED
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Investigations
WEIGHT DECREASED
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Metabolism and nutrition disorders
ACIDOSIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Metabolism and nutrition disorders
CACHEXIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.06%
1/1678
|
0.18%
3/1680
|
|
Metabolism and nutrition disorders
DIET REFUSAL
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Metabolism and nutrition disorders
ELECTROLYTE IMBALANCE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC CANCER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Musculoskeletal and connective tissue disorders
ARTHROPATHY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Musculoskeletal and connective tissue disorders
GROIN PAIN
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Musculoskeletal and connective tissue disorders
MUSCLE HAEMORRHAGE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Musculoskeletal and connective tissue disorders
OSTEOLYSIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Musculoskeletal and connective tissue disorders
OSTEOPOROTIC FRACTURE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Musculoskeletal and connective tissue disorders
POLYMYALGIA RHEUMATICA
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Musculoskeletal and connective tissue disorders
SPINAL PAIN
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA GASTRIC
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA OF COLON
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADRENAL GLAND CANCER
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-CELL LYMPHOMA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BRONCHIAL CARCINOMA
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CHRONIC MYELOID LEUKAEMIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER
|
0.06%
1/1678
|
0.12%
2/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
DIFFUSE LARGE B-CELL LYMPHOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
GASTRIC CANCER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HYPOPHARYNGEAL CANCER
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LARGE INTESTINE BENIGN NEOPLASM
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LARYNGEAL CANCER
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LARYNGEAL SQUAMOUS CELL CARCINOMA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA METASTATIC
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM MALIGNANT
|
0.18%
3/1678
|
0.36%
6/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT MESENCHYMOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO LIVER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MYELOID LEUKAEMIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM MALIGNANT
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NON-HODGKIN'S LYMPHOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NON-SMALL CELL LUNG CANCER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OESOPHAGEAL CARCINOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PENILE NEOPLASM
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PLASMA CELL MYELOMA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
|
0.24%
4/1678
|
0.12%
2/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RECTAL ADENOCARCINOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RECTAL CANCER
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RENAL CANCER
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SMALL CELL CARCINOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SMALL CELL LUNG CANCER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA OF LUNG
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TONGUE NEOPLASM MALIGNANT STAGE UNSPECIFIED
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
URETHRAL CANCER
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Nervous system disorders
BASAL GANGLIA STROKE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
BRAIN INJURY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Nervous system disorders
BRAIN STEM HAEMORRHAGE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
CAROTID ARTERIOSCLEROSIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Nervous system disorders
CAROTID ARTERY OCCLUSION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
CENTRAL NERVOUS SYSTEM LESION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
CEREBELLAR INFARCTION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
CEREBRAL INFARCTION
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Nervous system disorders
CEREBRAL ISCHAEMIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Nervous system disorders
CEREBRAL THROMBOSIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Nervous system disorders
CLUSTER HEADACHE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUSNESS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Nervous system disorders
DIZZINESS
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Nervous system disorders
EPILEPSY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Nervous system disorders
HEADACHE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
HEMIPARESIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
HYDROCEPHALUS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
ISCHAEMIC STROKE
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Nervous system disorders
LACUNAR INFARCTION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Nervous system disorders
SYNCOPE
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Nervous system disorders
VIITH NERVE PARALYSIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Psychiatric disorders
ANXIETY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Psychiatric disorders
COMPLETED SUICIDE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Psychiatric disorders
DELIRIUM TREMENS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Psychiatric disorders
DEPRESSION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Psychiatric disorders
HALLUCINATION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Psychiatric disorders
SLEEP DISORDER
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Renal and urinary disorders
CALCULUS URINARY
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Renal and urinary disorders
CHRONIC KIDNEY DISEASE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Renal and urinary disorders
URETHRAL STENOSIS
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Renal and urinary disorders
URINARY RETENTION
|
0.06%
1/1678
|
0.06%
1/1680
|
|
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Reproductive system and breast disorders
TESTICULAR TORSION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Reproductive system and breast disorders
UTERINE POLYP
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE PULMONARY OEDEMA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.30%
5/1678
|
0.24%
4/1680
|
|
Respiratory, thoracic and mediastinal disorders
ASTHMA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHITIS CHRONIC
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHOPLEURAL FISTULA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
10.8%
182/1678
|
12.3%
207/1680
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC RESPIRATORY FAILURE
|
0.24%
4/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/1678
|
0.12%
2/1680
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOTHORAX
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
HYPERCAPNIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
LARYNGEAL OEDEMA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
LUNG CONSOLIDATION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
PLEURISY
|
0.12%
2/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX
|
0.12%
2/1678
|
0.30%
5/1680
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX SPONTANEOUS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.24%
4/1678
|
0.12%
2/1680
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HAEMORRHAGE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HILAR ENLARGEMENT
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HYPERTENSION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY OEDEMA
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY ACIDOSIS
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.66%
11/1678
|
0.36%
6/1680
|
|
Skin and subcutaneous tissue disorders
LINEAR IGA DISEASE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Skin and subcutaneous tissue disorders
PARAPSORIASIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Skin and subcutaneous tissue disorders
SWELLING FACE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Vascular disorders
AORTIC ANEURYSM
|
0.12%
2/1678
|
0.18%
3/1680
|
|
Vascular disorders
AORTIC ANEURYSM RUPTURE
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Vascular disorders
AORTIC CALCIFICATION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Vascular disorders
ARTERIOSCLEROSIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Vascular disorders
CIRCULATORY COLLAPSE
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Vascular disorders
EMBOLISM ARTERIAL
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Vascular disorders
HYPERTENSION
|
0.18%
3/1678
|
0.12%
2/1680
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Vascular disorders
HYPOTENSION
|
0.12%
2/1678
|
0.00%
0/1680
|
|
Vascular disorders
LERICHE SYNDROME
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Vascular disorders
ORTHOSTATIC HYPOTENSION
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Vascular disorders
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
|
0.24%
4/1678
|
0.00%
0/1680
|
|
Vascular disorders
PERIPHERAL EMBOLISM
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Vascular disorders
TEMPORAL ARTERITIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Vascular disorders
THROMBOPHLEBITIS
|
0.06%
1/1678
|
0.00%
0/1680
|
|
Vascular disorders
THROMBOSIS
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Vascular disorders
VARICOSE ULCERATION
|
0.00%
0/1678
|
0.06%
1/1680
|
|
Vascular disorders
VENOUS THROMBOSIS
|
0.06%
1/1678
|
0.00%
0/1680
|
Other adverse events
| Measure |
QVA149
n=1678 participants at risk
QVA149 (110/50 μg) once daily
|
Long Acting B2 Agonist (LABA) and Inhaled Corticosteroid (ICS)
n=1680 participants at risk
Salmeterol/fluticasone (50/500μg) twice a day
|
|---|---|---|
|
Gastrointestinal disorders
CONSTIPATION
|
1.1%
19/1678
|
1.0%
17/1680
|
|
Gastrointestinal disorders
DIARRHOEA
|
1.1%
19/1678
|
1.4%
24/1680
|
|
Gastrointestinal disorders
DYSPEPSIA
|
1.1%
18/1678
|
0.54%
9/1680
|
|
Gastrointestinal disorders
GASTRITIS
|
0.60%
10/1678
|
1.2%
20/1680
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
1.2%
20/1678
|
0.65%
11/1680
|
|
General disorders
OEDEMA PERIPHERAL
|
1.5%
26/1678
|
0.77%
13/1680
|
|
General disorders
PYREXIA
|
1.0%
17/1678
|
1.6%
27/1680
|
|
Infections and infestations
BRONCHITIS
|
1.7%
29/1678
|
2.4%
41/1680
|
|
Infections and infestations
GASTROENTERITIS
|
0.60%
10/1678
|
1.1%
18/1680
|
|
Infections and infestations
INFLUENZA
|
2.0%
34/1678
|
3.3%
55/1680
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
4.5%
76/1678
|
5.4%
91/1680
|
|
Infections and infestations
NASOPHARYNGITIS
|
11.7%
197/1678
|
11.5%
194/1680
|
|
Infections and infestations
ORAL CANDIDIASIS
|
1.2%
20/1678
|
4.2%
71/1680
|
|
Infections and infestations
OROPHARYNGEAL CANDIDIASIS
|
0.12%
2/1678
|
1.0%
17/1680
|
|
Infections and infestations
PNEUMONIA
|
1.1%
19/1678
|
1.6%
27/1680
|
|
Infections and infestations
RESPIRATORY TRACT INFECTION VIRAL
|
1.0%
17/1678
|
0.48%
8/1680
|
|
Infections and infestations
RHINITIS
|
1.6%
27/1678
|
1.7%
28/1680
|
|
Infections and infestations
SINUSITIS
|
0.95%
16/1678
|
1.2%
20/1680
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
4.7%
79/1678
|
4.9%
82/1680
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
|
7.2%
121/1678
|
9.3%
157/1680
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.83%
14/1678
|
1.3%
22/1680
|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
7.8%
131/1678
|
8.1%
136/1680
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
1.2%
20/1678
|
1.4%
23/1680
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
2.1%
35/1678
|
2.0%
34/1680
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
1.0%
17/1678
|
0.77%
13/1680
|
|
Nervous system disorders
DIZZINESS
|
0.36%
6/1678
|
1.6%
27/1680
|
|
Nervous system disorders
HEADACHE
|
2.3%
38/1678
|
2.0%
34/1680
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
75.2%
1262/1678
|
79.2%
1331/1680
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
3.0%
50/1678
|
2.9%
49/1680
|
|
Respiratory, thoracic and mediastinal disorders
DYSPHONIA
|
0.42%
7/1678
|
1.8%
30/1680
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
2.4%
41/1678
|
2.8%
47/1680
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
2.1%
35/1678
|
2.0%
33/1680
|
|
Respiratory, thoracic and mediastinal disorders
SPUTUM INCREASED
|
0.60%
10/1678
|
1.4%
23/1680
|
|
Vascular disorders
HYPERTENSION
|
2.6%
44/1678
|
2.4%
40/1680
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER