Comparison of Long-term Safety of the Combination Product... | NCT01610037

NCT01610037

ID	Type	Description	Link
2012-002057-38	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Intervention Names
QVA149	Experimental	Drug: QVA149
Tiotropium	Active Comparator	Drug: Tiotropium
placebo	Placebo Comparator	Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
QVA149	Drug	QVA149 110/50 µg will be supplied as capsules in blister packs for once daily inhalation using the Novartis Concept1 SDDPI	QVA149

Outcomes Module

Measure	Description	Time Frame
Number of Patients With Serious Adverse Events	The overall rate of serious adverse events reported from initiation through 30 days post last dose.	Week 52

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients With Composite Endpoint of All-cause Mortality, and Serious Cardio- and Cerebrovascular (CCV) Events.	The endpoint of all-cause mortality and serious CCV events (composite) was chosen to further characterize any discernible risks. The patients with an event in the analysis were those who had at least one of the 2 events namely, all-cause mortality and serious CCV, during treatment or within 30 days after the date of last dose of study drug.

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Buenos Aires	Buenos Aires	1425	Argentina
Novartis Investigative Site

Results Section

Participant Flow Module

ID	Title	Description
FG000	QVA149	110/50 µg capsules for inhalation, o.d
FG001	Tiotropium	18 μg capsules for inhalation, o.d

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	QVA149	110/50 µg capsules for inhalation, o.d
BG001	Tiotropium	18 μg capsules for inhalation, o.d
BG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG00055 OG00155 OG00250

Secondary

Percentage of Patients With Composite Endpoint of All-cause Mortality, and Serious Cardio- and Cerebrovascular (CCV) Events.

The endpoint of all-cause mortality and serious CCV events (composite) was chosen to further characterize any discernible risks. The patients with an event in the analysis were those who had at least one of the 2 events namely, all-cause mortality and serious CCV, during treatment or within 30 days after the date of last dose of study drug.

The full analysis set (FAS) included all randomized patients who received at least one dose of study drug. Patients were analyzed according to the treatment they were assigned to at randomization. If the patient was assigned to the wrong stratum for randomization, the patient was analyzed according to the actual (rather than assigned) stratum.

Posted

Number

Percentage of participants

52 weeks

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Secondary

Post-hoc Analysis: Percentage of Patients With Composite Endpoint of Cardiovascular Death and MACE

The composite endpoint included all deaths and all serious CCV events, including MACE and events which were not considered MACE. A rigorous post hoc analysis was done on composite endpoint of CV deaths and major adverse cardiovascular events (MACE). The patients with an event in the analysis were those who had at least one of the 2 events namely, CV deaths and MACE, during treatment or within 30 days after the date of last dose of study drug.

Posted

Number

Percentage of participants

52 weeks

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Secondary

Change From Baseline in Pre-Dose Forced Expiratory Volume Over in Second (FEV1)

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.

The full analysis set (FAS) included all randomized patients who eceived at least one dose of study drug. Patients were analyzed according to the treatment they were assigned to at randomization. If the patient was assigned to the wrong stratum for randomization, the patient was analyzed according to the actual (rather than assigned) stratum

Posted

Least Squares Mean

Standard Error

Liters

Day 22, 43, 85, 183, 274 and 364

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Secondary

Change From Baseline in Health Status as Measured by St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C)

The SGRQ-C contains 40 items divided into two parts covering three aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts" which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score will be calculated for each of these three subscales and a "Total" score will also be calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.

Posted

Mean

Standard Deviation

Score

Measurment at day 364

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d

Secondary

Change From Baseline in Daily, Morning and Evening Symptom Scores

Patients will be provided with an electronic diary (eDiary) to record daily clinical symptoms, or rescue medication. The patients will be instructed to routinely complete the patient diary twice daily. There are 9 total symptom questions for a total possible score of 27 at each timepoint. A higher score means the patient is reporting more symptoms related to Chronic Obstructive Pulmonary Disease. The mean daily total symptom score, the mean daytime total symptom score and the mean nighttime total symptom score were calculated for each patient over 52 weeks. Diary data recorded during the 14 day run-in period were used to calculate the baseline.

Posted

Mean

Standard Deviation

Score

52 weeks

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo

Secondary

Change From Baseline in Percentage of Nights With 'no Nighttime Awakenings

A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms.

Posted

Mean

Standard Deviation

Percentage of nights

52 weeks

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Units	Counts

Secondary

Change From Baseline in Percentage of no Daytime Symptoms

A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) during the past 12 hours (approx. 8 am to 8 pm).

Posted

Mean

Standard Deviation

Percentage of days

52 weeks

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Secondary

Change From Baseline in Percentage of Days Able to Perform Usual Daily Activities.

A day able to perform usual daily activities' is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms.

Posted

Mean

Standard Deviation

Percentage of days

52 weeks

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Units

Secondary

Change From Baseline in 1 Hour Post-dose Forced Vital Capacity (FVC) Measurements

Pulmonary function assessments were performed using centralized spirometry according to international standards

Posted

Mean

Standard Deviation

Liters

Day 1, 22, 43, 85, 183, 274 and 364

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Units	Counts

Secondary

Time to Premature Discontinuation

Time to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment early. The range of the 'time to treatment discontinuation' varied from 5-407 days in the Tiotropium group. Hence the model estimated lower limit of the median time to treatment discontinuation is greater than the scheduled treatment period of 52 weeks.

The Safety set consisted of 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.

Posted

Median

95% Confidence Interval

Days

Time varied from 5 - 407 days

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Secondary

Change From Baseline in 1 Hour Post-dose FEV1 Measurements

The avg 60 min post dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.

Posted

Mean

Standard Deviation

Liters

Day 1, 22, 43, 85, 183, 274 and 364

ID	Title	Description
OG000	QVA149	110/50 µg capsules for inhalation, o.d
OG001	Tiotropium 18 µg o.d	18 μg capsules for inhalation, o.d
OG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d

Units	Counts

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	QVA 149	110/50 µg capsules for inhalation, o.d	55	407	294	407
EG001	Tiotropium	18 μg capsules for inhalation, o.d	55	405	294	405
EG002	Placebo	To match QVA149 capsules for inhalation, o.d To match tiotropium capsules for inhalation, o.d	50	403	309	403

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Angina unstable	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0003 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Cardiac arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Cardiac failure acute	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0013 affected405 at risk EG0020 affected403 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Cor pulmonale	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Sudden hearing loss	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Cataract	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0012 affected405 at risk EG0020 affected403 at risk
Abdominal mass	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Mesenteric artery thrombosis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Pancreatitis haemorrhagic	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Hypothermia	General disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Cholangitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0022 affected403 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Hepatic mass	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Liver injury	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Acute sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Arthritis bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Breast abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Bronchitis bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Bronchopneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Gastroenteritis salmonella	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Lobar pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0012 affected405 at risk EG0022 affected403 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected407 at risk EG0016 affected405 at risk EG0022 affected403 at risk
Pneumonia bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Skin infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0022 affected403 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0012 affected405 at risk EG0020 affected403 at risk
Acetabulum fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Pneumothorax traumatic	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0012 affected405 at risk EG0020 affected403 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Traumatic haemothorax	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0002 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Arteriogram coronary	Investigations	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Hepatic enzyme increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Transaminases increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Adenocarcinoma gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Adenolipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Hepatic cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Hypopharyngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Malignant mediastinal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0012 affected405 at risk EG0020 affected403 at risk
Mantle cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Metastases to lymph nodes	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0002 affected407 at risk EG0012 affected405 at risk EG0021 affected403 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Optic neuritis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Radiculitis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
VIth nerve paresis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Vertebrobasilar insufficiency	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Aggression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Alcoholism	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Suicide attempt	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Urinary retention	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Bronchial disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00020 affected407 at risk EG00118 affected405 at risk EG00223 affected403 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0013 affected405 at risk EG0020 affected403 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected407 at risk EG0011 affected405 at risk EG0021 affected403 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0011 affected405 at risk EG0020 affected403 at risk
Aortic aneurysm	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0003 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Hypertensive crisis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Iliac artery occlusion	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Ischaemia	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk
Jugular vein distension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected407 at risk EG0010 affected405 at risk EG0020 affected403 at risk
Peripheral artery thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected407 at risk EG0010 affected405 at risk EG0021 affected403 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0007 affected407 at risk EG00111 affected405 at risk EG00218 affected403 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00022 affected407 at risk EG00114 affected405 at risk EG00219 affected403 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00033 affected407 at risk EG00131 affected405 at risk EG00226 affected403 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected407 at risk EG00111 affected405 at risk EG0027 affected403 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00018 affected407 at risk EG00122 affected405 at risk EG00218 affected403 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG00027 affected407 at risk EG00128 affected405 at risk EG00225 affected403 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00019 affected407 at risk EG00113 affected405 at risk EG00217 affected403 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00010 affected407 at risk EG0016 affected405 at risk EG0026 affected403 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0009 affected407 at risk EG00113 affected405 at risk EG00211 affected403 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG000269 affected407 at risk EG001274 affected405 at risk EG002287 affected403 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00017 affected407 at risk EG00121 affected405 at risk EG00218 affected403 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0008 affected407 at risk EG0017 affected405 at risk EG00212 affected403 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0009 affected407 at risk EG00110 affected405 at risk EG00213 affected403 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
D000069447	Tiotropium Bromide

ID	Term
D012602	Scopolamine Derivatives
D014326	Tropanes
D053961	Azabicyclo Compounds
D001372	Aza Compounds
D009930	Organic Chemicals
D000470	Alkaloids
D006571	Heterocyclic Compounds
D019086	Bridged Bicyclo Compounds, Heterocyclic
D006572	Heterocyclic Compounds, Bridged-Ring