Effect of QVA149 Versus NVA237 and Tiotropium on Chronic... | NCT01120691

ID	Type	Description	Link
2009-013256-69	EudraCT Number

Label	Type	Description	Intervention Names
QVA149	Experimental	QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.	Drug: QVA149 Drug: Salbutamol/albuterol
NVA237	Active Comparator	NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.	Drug: NVA237 Drug: Salbutamol/albuterol
open-label tiotropium	Active Comparator	Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.	Drug: tiotropium Drug: Salbutamol/albuterol

Name	Type	Description	Arm Group Labels	Other Names
QVA149	Drug	QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and NVA237 Treatment Arms During the Treatment Period.	A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as a worsening of two or more of the following major symptoms for at least 2 consecutive days: dyspnea, sputum volume or sputum purulence OR a worsening of any 1 major symptom together with an increase in any 1 of the following minor symptoms for at least 2 consecutive days: sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough or wheezing. A COPD exacerbation was considered of moderate severity if treatment with systemic glucocorticosteroids or antibiotics or both was required and severe if hospitalization was required. An emergency room (ER) visit of longer than 24 hours was considered a hospitalization. Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years	64 weeks

Secondary Outcomes

Measure	Description	Time Frame
Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and Open-label Tiotropium Treatment Arms During the Treatment Period.	A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as a worsening of two or more of the following major symptoms for at least 2 consecutive days: dyspnea, sputum volume or sputum purulence OR a worsening of any 1 major symptom together with an increase in any 1 of the following minor symptoms for at least 2 consecutive days: sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough or wheezing. A COPD exacerbation was considered of moderate severity if treatment with systemic glucocorticosteroids or antibiotics or both was required and severe if hospitalization was required. An emergency room (ER) visit of longer than 24 hours was considered a hospitalization. Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years

Eligibility Module

Eligibility Criteria

Inclusion Criteria :

Male or female adults aged ≥40 years, who had signed an informed consent form prior to initiation of any study-related procedure.
Patients with severe to very severe Chronic Obstructive Pulmonary Disease COPD (Stage III or IV) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2008.
Current or ex-smokers with a smoking history of at least 10 pack years (Ten pack-years were defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years).
Patients with a post-bronchodilator Forced Expiratory Volume in one second ( FEV1) <50% of the predicted normal value, and post-bronchodilator FEV1/ Forced Vital Capacity (FVC) <0.70 at Visit 2 (day -14). (Post refers to 1 h after sequential inhalation of 84 µg (or equivalent dose) of ipratropium bromide and 400 µg of salbutamol).
A documented history of at least 1 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticosteroids and/or antibiotics.

Exclusion Criteria:

Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
Women of child-bearing potential
Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic hypoxemia.
Patients who had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to visit 1 or between visit 1 (Day -21) and Visit 3 (Day 1).
Patients who developed a COPD exacerbation during a period between visit 1 and 3 were ineligible but were permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
Patients who had a respiratory tract infection within 4 weeks prior to visit 1 (Day -21)

• Patients who developed an upper or lower respiratory tract infection during the screening period (up to visit 3 (Day 1) were not eligible, but were permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection
Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), clinically significant bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension.
Patients with lung lobectomy, or lung volume reduction or lung transplantation.
Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to):
- Unstable ischemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding chronic stable Atrial Fibrillation (AF). Patients with such events not considered clinically significant by the investigator may be considered for inclusion in the study
- history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
- uncontrolled hypo- or hyperthyroidism, hypokalemia or hyper adrenergic state
- narrow-angle glaucoma
- Symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (Patients with a Transurethral Resection of Prostate (TURP) were excluded from the study. Patients who underwent full re-section of the prostate could be considered for the study, as well as patients who were asymptomatic and stable on pharmacological treatment for the condition).
- any condition which might have compromised patient safety or compliance, interfered with evaluation, or precluded completion of the study
Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count > 600/mm3 (at visit 2), or onset of symptoms prior to 40 years. Patients without asthma were excluded if their eosinophil count was >600/mm3 at visit 2.
Patients with allergic rhinitis who used H1 antagonists or intranasal corticosteroids intermittently (treatment with a constant dose was permitted).
Patients with eczema (atopic), known high immunoglobulin E (IgE) levels or a known positive skin prick test in the last 5 years.
Patients with known history and diagnosis of alpha-1 antitrypsin deficiency.
Patients who were participating in the active phase of a supervised pulmonary rehabilitation program.
Patients with Type I or uncontrolled Type II diabetes.
Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs or drugs of a similar class or any component thereof:
- anticholinergic agents
- long and short acting beta-2 agonists
- sympathomimetic amines.
Patients with a history of long QT syndrome or whose corrected QT interval (QTc) measured at visit 2 (Day -14) (Fridericia method) was prolonged (>450 ms for males and females) as confirmed by the central ECG assessor.
Patients with a clinically significant abnormality on the screening or baseline ECG who in the judgment of the investigator would be at potential risk if enrolled into the study. (These patients could not be re-screened).
Patients who needed treatments for COPD and allied conditions after the start of the study (visit 1)
Patients who needed treatments for COPD and allied conditions (e.g. allergic rhinitis) unless they had been stabilized
Patients taking other prohibited medications
Patients unable to use a dry powder inhaler (e.g. single dose dry powder inhaler (SDDPI), HandiHaler® device, or pressurized Metered Dose Inhaler (MDI) (rescue medication).
Patients unable to use an electronic patient diary.
Patients who were, in the opinion of the investigator known to be unreliable or non-compliant.
Patients who used other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of visit 1 (day -21), whichever was longer.
Patients who had live attenuated vaccination within 30 days prior to the screening visit or during the run-in period. Inactivated influenza vaccination, pneumococcal vaccination or any other inactivated vaccine was acceptable provided it was not administered within 48 hours prior to screening and randomization visits.

No additional exclusions were applied by the investigator, in order to ensure that the study population was representative of all eligible patients.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Birmingham	Alabama	35233	United States
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
24429126	Derived	Wedzicha JA, Decramer M, Ficker JH, Niewoehner DE, Sandstrom T, Taylor AF, D'Andrea P, Arrasate C, Chen H, Banerji D. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respir Med. 2013 May;1(3):199-209. doi: 10.1016/S2213-2600(13)70052-3. Epub 2013 Apr 23.

ID	Title	Description
FG000	QVA149	QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period. Salbutamol/albuterol was available for rescue medication use throughout the study.
FG001	NVA237

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and NVA237 Treatment Arms During the Treatment Period.

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

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

Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site , which had major issues with Good Clinical Practice (GCP) compliance.

Posted

Number

Exacerbations per year

64 weeks

Moderate to Severe COPD Exacerbation

Participants

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237	NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Units	Counts
Participants	OG000729 OG001739
Moderate to Severe COPD Exacerbation	OG000812 OG001

Title

Denominators

Categories

Title	Measurements
	OG0000.94 OG0011.07

Secondary

Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and Open-label Tiotropium Treatment Arms During the Treatment Period.

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

Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site, which had major issues with GCP compliance.

Posted

Number

Exacerbations per year

76 weeks

Moderate to Severe COPD Exacerbation

Participants

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

Time to First Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Between QVA149, NVA237 and Open Label Tiotropium During the Treatment Period

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

Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site, which had major issues with GCP compliance. Only patients with a moderate or severe COPD exacerbation were included in this analysis.

Posted

Median

95% Confidence Interval

days

64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Requiring the Use of Both Systemic Glucocorticosteroids and Antibiotics

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

Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site, which had major issues with GCP compliance. The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug and data was available for analysis.

Posted

Number

exacerbations per year

64 weeks

exacerbations

Participants

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237	NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG002

Secondary

Number of Days With Moderate or Severe Exacerbation That Required Treatment With Systemic Corticosteroids and Antibiotics

The number of exacerbation days is defined as the sum of the duration of days recorded as an exacerbation for all exacerbations recorded per patient.

Modified Full Analysis Set (mFAS) included all patients in the Full analysis set except patients from a site with GCP non-compliance. This is a sub-group analysis with mutually exclusive population in each category for analysis.

Posted

Mean

Standard Deviation

Days

64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237	NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG002	Open-label Tiotropium

Secondary

Time to Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.) During the Treatment Period.

Time to Study Withdrawal or Premature Discontinuation for Any Reason was analyzed for each treatment group using a Kaplan-Meier estimation for the modified safety set. Patients who did not discontinue early were censored at the final visit of the treatment phase.

Modified safety set (mSAF set) includes all patients in the safety set except patients from a site who had major GCP issues. The Safety set includes all patients who received at least one dose of study drug whether or not being randomized. Analysis population included patients with study withdrawal or premature discontinuation for any reason.

Posted

Median

95% Confidence Interval

days

64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237	NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

Percentage of Patients With Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.)During the Treatment Period

Percentage of Patients With Study Withdrawal or Premature Discontinuation for Any Reason was analyzed for each treatment group using a Kaplan-Meier estimation for the modified safety set. Patients who did not discontinue early were censored at the final visit of the treatment phase.

Posted

Number

percentage of participants

64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237	NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

Cumulative Rates of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations for Multiple COPD Exacerbation at Different Time Points

Cumulative rates were estimated using Anderson and Gill method. Chronic Obstructive Pulmonary Disease (COPD) exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if treatment for moderate severity and hospitalization were required. Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years

Modified Full Analysis Set(mFAS) included all patients in the Full Analysis Set (FAS) except patients from a site, which had major issues with GCP compliance. FAS include all randomized patients who received at least one dose of study drug and data was available for analysis.

Posted

Number

95% Confidence Interval

exacerbations per year

26, 52, 64, 76 weeks

Moderate or Severe COPD Exacerbations

Participants

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237	NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

Pre-dose Forced Expiratory Volume in 1 Second (FEV-1) After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium

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

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

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

Posted

Least Squares Mean

Standard Error

L (liters)

4, 12, 26, 38, 52 and 64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

Pre-dose Forced Vital Capacity (FVC)After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium

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

Posted

Least Squares Mean

Standard Error

L (liters)

4, 12, 26, 38, 52 and 64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237

Secondary

Change in Mean Daily Use (Number of Puffs) of Rescue Therapy Between QVA149, NVA237 and Open Label Tiotropium From Baseling Over the 64 Week Treatment Period

The severe or less FEV1 % predicted (post bronchodilator)>=30%; very severe=> FEV1 % predicted(the post bronchodilator)<30%.Number of puffs of rescue medication taken in the previous 12 hours was recorded in patient diary in the morning and in the evening for 26 weeks.The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient.Rescue medication data recorded during the 14 day run-in was used to calculate the baseline.A negative change from baseline indicates improvement. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates.

Modified Full Analysis Set mFAS included all patients in the Full analysis set except patients from a site,which had major issues with GCP compliance. The Full Analysis Set includes all randomized patients who received at least one dose of study drug and data was available for analysis. Patients with evaluable data were included in this analysis

Posted

Least Squares Mean

Standard Error

# puffs

Baseline (14 day run-in), 64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

Change From Baseline of Percentage of Days Without Rescue Therapy Use Between QVA149,NVA237 and Open Label Tiotropium Over the 64 Week Treatment Period

A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. The percentage of days is calculated by the number of days with no rescue medicine use/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.

Modified Full Analysis Set(mFAS)included all patients in the Full analysis set except patients from a site,which had major issues with GCP compliance. The Full Analysis Set includes all randomized patients who received at least one dose of study drug and data was available for analysis. Patients with evaluable data were included in this analysis

Posted

Least Squares Mean

Standard Error

percentage of days

Baseline (14 day run-in), 64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.

Secondary

St. George's Respiratory Questionnaire (SGRQ) Scores Between QVA149, NVA237 and Open Label Tiotropium Over 12, 26, 38, 52 and 64 Weeks of Treatment

St. George's Respiratory Questionnaire (SGRQ) is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. Mixed model used baseline SGRQ, baseline inhaled corticosteroid (ICS) use, Forced Expiratory Volume in 1 Second (FEV1) prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates. SGRQ total score is the sum of the scores from the three components; symptoms, activity and impacts.

Posted

Least Squares Mean

Standard Error

units on a scale

12, 26, 38, 52 and 64 weeks

ID	Title	Description
OG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI)for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
OG001	NVA237

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Idiopathic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0014 affected740 at risk EG0022 affected737 at risk
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0013 affected740 at risk EG0021 affected737 at risk
Angina unstable	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0006 affected729 at risk EG0013 affected740 at risk EG0024 affected737 at risk
Atrial flutter	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0021 affected737 at risk
Cardiac arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0014 affected740 at risk EG0022 affected737 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0024 affected737 at risk
Cardiac failure acute	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0013 affected740 at risk EG0023 affected737 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cor pulmonale	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0013 affected740 at risk EG0020 affected737 at risk
Cor pulmonale chronic	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0003 affected729 at risk EG0012 affected740 at risk EG0021 affected737 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Left ventricular hypertrophy	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0013 affected740 at risk EG0024 affected737 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pericardial effusion	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pericarditis	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Right ventricular failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Supraventricular tachyarrhythmia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Congenital laryngeal stridor	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Phimosis	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Acute vestibular syndrome	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Goitre	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Angle closure glaucoma	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cataract	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Retinal detachment	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Vision blurred	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Duodenal ulcer perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Enteritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Food poisoning	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Gastric disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Intestinal congestion	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Intestinal polyp	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Oesophageal ulcer haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pancreatic mass	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Peptic ulcer haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Adverse drug reaction	General disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Chills	General disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Cyst	General disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Death	General disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Generalised oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Multi-organ failure	General disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0012 affected740 at risk EG0023 affected737 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0011 affected740 at risk EG0022 affected737 at risk
Sudden cardiac death	General disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Sudden death	General disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Thrombosis in device	General disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Hepatitis alcoholic	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Allergy to arthropod sting	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Abscess intestinal	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Abscess rupture	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Anal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0012 affected740 at risk EG0021 affected737 at risk
Appendicitis perforated	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected729 at risk EG0012 affected740 at risk EG0025 affected737 at risk
Bronchopneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cholecystitis infective	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Haemophilus infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Kidney infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Laryngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Lobar pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00014 affected729 at risk EG00124 affected740 at risk EG00213 affected737 at risk
Lower respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0015 affected740 at risk EG0021 affected737 at risk
Lower respiratory tract infection fungal	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Lower respiratory tract infection viral	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Lung infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Lung infection pseudomonal	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Oropharyngeal candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Otitis media acute	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Otitis media chronic	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Perineal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Peritonitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG00023 affected729 at risk EG00125 affected740 at risk EG00224 affected737 at risk
Pneumonia bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pneumonia legionella	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Pneumonia primary atypical	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Rabies	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0022 affected737 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Scrotal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0013 affected740 at risk EG0020 affected737 at risk
Septic shock	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Subcutaneous abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG00020 affected729 at risk EG00120 affected740 at risk EG00210 affected737 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected729 at risk EG0015 affected740 at risk EG0023 affected737 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Incisional hernia	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pneumothorax traumatic	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Postoperative ileus	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Blood pressure increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Electrocardiogram abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Intraocular pressure increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0003 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Compartment syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Osteochondritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Adrenal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Breast cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Bronchial carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0022 affected737 at risk
Carcinoid tumour of the caecum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Gliosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Laryngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0022 affected737 at risk
Laryngeal cancer stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0003 affected729 at risk EG0010 affected740 at risk EG0024 affected737 at risk
Lung squamous cell carcinoma stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Mediastinum neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Oesophageal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Pancreatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Prostatic adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0022 affected737 at risk
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Small cell lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Small intestine carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Ataxia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cerebellar syndrome	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Cerebral infarction	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0023 affected737 at risk
Cerebrovascular disorder	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Cerebrovascular insufficiency	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Cervicobrachial syndrome	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Epilepsy	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Grand mal convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Ischaemic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Lethargy	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Loss of consciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Monoparesis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Movement disorder	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Completed suicide	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Delirium	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Hallucination	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Major depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Mental status changes	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Psychotic disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Acute prerenal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Bladder dysfunction	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0012 affected740 at risk EG0020 affected737 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Renal colic	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Urinary retention	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Epididymitis	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0007 affected729 at risk EG0016 affected740 at risk EG0021 affected737 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG000107 affected729 at risk EG001116 affected740 at risk EG00287 affected737 at risk
Chronic respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0005 affected729 at risk EG0012 affected740 at risk EG0023 affected737 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Foreign body aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0012 affected740 at risk EG0021 affected737 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0013 affected740 at risk EG0021 affected737 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Lung consolidation	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0021 affected737 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0015 affected740 at risk EG0021 affected737 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pulmonary air leakage	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected729 at risk EG0013 affected740 at risk EG0021 affected737 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0022 affected737 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0005 affected729 at risk EG0017 affected740 at risk EG0026 affected737 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Vocal cord inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Pollution	Social circumstances	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Coronary arterial stent insertion	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Aortic aneurysm	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Aortic aneurysm rupture	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Arterial occlusive disease	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0022 affected737 at risk
Arterial stenosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0011 affected740 at risk EG0020 affected737 at risk
Arteriosclerosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Deep vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0012 affected740 at risk EG0022 affected737 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Iliac artery stenosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Peripheral artery aneurysm	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Peripheral ischaemia	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected729 at risk EG0010 affected740 at risk EG0021 affected737 at risk
Phlebitis deep	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk
Shock haemorrhagic	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected729 at risk EG0010 affected740 at risk EG0020 affected737 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0003 affected729 at risk EG0018 affected740 at risk EG0023 affected737 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected729 at risk EG00111 affected740 at risk EG0029 affected737 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0007 affected729 at risk EG0017 affected740 at risk EG0028 affected737 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0008 affected729 at risk EG00111 affected740 at risk EG0024 affected737 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00021 affected729 at risk EG00111 affected740 at risk EG00215 affected737 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected729 at risk EG00113 affected740 at risk EG00216 affected737 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00013 affected729 at risk EG00110 affected740 at risk EG00215 affected737 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00012 affected729 at risk EG0015 affected740 at risk EG00212 affected737 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected729 at risk EG0014 affected740 at risk EG0029 affected737 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected729 at risk EG00112 affected740 at risk EG0024 affected737 at risk
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected729 at risk EG0014 affected740 at risk EG0026 affected737 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0004 affected729 at risk EG0018 affected740 at risk EG0023 affected737 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG00014 affected729 at risk EG00111 affected740 at risk EG0029 affected737 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG00022 affected729 at risk EG00118 affected740 at risk EG00216 affected737 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG00026 affected729 at risk EG00124 affected740 at risk EG00222 affected737 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG00032 affected729 at risk EG00136 affected740 at risk EG00226 affected737 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG00023 affected729 at risk EG00122 affected740 at risk EG00219 affected737 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00049 affected729 at risk EG00168 affected740 at risk EG00269 affected737 at risk
Lower respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected729 at risk EG0018 affected740 at risk EG0024 affected737 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00098 affected729 at risk EG00181 affected740 at risk EG00290 affected737 at risk
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG00011 affected729 at risk EG00110 affected740 at risk EG00212 affected737 at risk
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00017 affected729 at risk EG00111 affected740 at risk EG00210 affected737 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG00011 affected729 at risk EG00113 affected740 at risk EG00210 affected737 at risk
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG0009 affected729 at risk EG00110 affected740 at risk EG0026 affected737 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG00012 affected729 at risk EG00120 affected740 at risk EG00221 affected737 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00026 affected729 at risk EG00125 affected740 at risk EG00228 affected737 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG000119 affected729 at risk EG001123 affected740 at risk EG002109 affected737 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00027 affected729 at risk EG00119 affected740 at risk EG00215 affected737 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00070 affected729 at risk EG00175 affected740 at risk EG00272 affected737 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0009 affected729 at risk EG0014 affected740 at risk EG0024 affected737 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00014 affected729 at risk EG00111 affected740 at risk EG00211 affected737 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0009 affected729 at risk EG0014 affected740 at risk EG0027 affected737 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00012 affected729 at risk EG0019 affected740 at risk EG0025 affected737 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00012 affected729 at risk EG00110 affected740 at risk EG00210 affected737 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00024 affected729 at risk EG00133 affected740 at risk EG00236 affected737 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected729 at risk EG0019 affected740 at risk EG0029 affected737 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00012 affected729 at risk EG0019 affected740 at risk EG0026 affected737 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0009 affected729 at risk EG0018 affected740 at risk EG0025 affected737 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG00013 affected729 at risk EG00112 affected740 at risk EG0028 affected737 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00030 affected729 at risk EG00133 affected740 at risk EG00239 affected737 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0004 affected729 at risk EG0012 affected740 at risk EG0029 affected737 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG000618 affected729 at risk EG001639 affected740 at risk EG002629 affected737 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00040 affected729 at risk EG00139 affected740 at risk EG00225 affected737 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected729 at risk EG0015 affected740 at risk EG0029 affected737 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00021 affected729 at risk EG00142 affected740 at risk EG00232 affected737 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00025 affected729 at risk EG00132 affected740 at risk EG00229 affected737 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0007 affected729 at risk EG00113 affected740 at risk EG0028 affected737 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0005 affected729 at risk EG0019 affected740 at risk EG0023 affected737 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG00030 affected729 at risk EG00120 affected740 at risk EG00224 affected737 at risk

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C554862	indacaterol-glycopyrronium combination
D006024	Glycopyrrolate
D000069447	Tiotropium Bromide
D000420	Albuterol

ID	Term
D000644	Quaternary Ammonium Compounds
D000588	Amines
D009930	Organic Chemicals
D009861	Onium Compounds
D011759	Pyrrolidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D012602	Scopolamine Derivatives
D014326	Tropanes
D053961	Azabicyclo Compounds
D001372	Aza Compounds
D000470	Alkaloids
D019086	Bridged Bicyclo Compounds, Heterocyclic
D006572	Heterocyclic Compounds, Bridged-Ring
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D010627	Phenethylamines
D005021	Ethylamines

ID	Title	Description
BG000	QVA149	QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period. Salbutamol/albuterol was available for rescue medication use throughout the study.
BG001	NVA237	NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period. Salbutamol/albuterol was available for rescue medication use throughout the study.
BG002	Open-label Tiotropium	Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	QVA149	QVA149 : QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.	167	729	656	729
EG001	NVA237	NVA237 : NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.	179	740	671	740
EG002	Open-label Tiotropium	Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device. for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.	165	737	666	737