ENLIGHTEN: A Study to Assess the Long-term Safety of QVA149

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01120717
• Collaborator: (none)
• Enrollment: 339
• Locations: 53
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The study is designed to provide long-term safety data for QVA149 in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: QVA149; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 339 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicener, Randomised, Double-blind, Placebo-controlled Study, to Assess the Long Term Safety of 52 Weeks Treatment With QVA149 (110 ug Indacaterol/50ug Glycopyrrolate) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QVA149 110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Drug: QVA149; capsules for inhalation, delivered by an SDDPI
Placebo Comparator: Placebo Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI	Drug: Placebo; capsules for inhalation, delivered by an SDDPI

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events, Serious Adverse Events or Death [52 weeks + Follow-up (Up to Day 394)]

   Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.

Secondary Outcome Measures

1. Pre-dose FEV1 [52 weeks]

   Pre-dose FEV1 is defined as the average of the FEV1 15 minutes pre-dose and FEV1 45 minutes pre-dose. A mixed model was used with treatment as a fixed effect, average of 15 min and 45 min pre-dose FEV1 at visit 3 as the baseline measurement, and FEV1 prior to inhalation and FEV1 60 min post inhalation of two short acting bronchodialators as covariates. The model also included smoking status at baseline, history of ICS use and country as fixed effects with center nested within country as a random effect.

2. Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

   Clinically notable hematology values were: hemoglobin - male <115g/L, female <95 g/L; hematocrit - male <0.37v/v, female <0.32v/v; white cell count - <2.8 10E9/L or >16.0 10E9/L; platelets - <75 10E9/L or >700 10E9/L

3. Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

   Clinically notable biochemistry values were: sodium <125mmol/L or >160mmol/L; potassium <3.0mmol/L or >6.0mmol/L; BUN >9.99mmol/L; creatinine >176.8µmol/L; total protein (serum) <40g/L or >95g/L; albumin <25g/L; bilirubin (total) >34.2µmol/L; SGPT >3 x ULN; SGOT > 3 x ULN; gamma glutamyltransferase >3 x ULN; alkaline phosphatase (serum) >3 x ULN; glucose <2.78mmol/L or >9.99mmol/L

4. Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

   Clinically notable vital sign values were: pulse rate - low, <40 bpm or <=50 bpm and decrease from baseline >=15bpm; pulse rate high, >130 bpm or >=120bpm and increase from baseline >=15 bpm. Systolic blood pressure - low, <75 mmHg or <=90 mmHg and decrease from baseline >=20 mmHg; high, >200 mmHg or >=180 mmHg and increase from baseline >=20 mmHg. Diastolic blood pressure - low, <40 mmHg or <=50 mmHg and decrease from baseline >=15 mmHg; high, >115 mmHg or >=105 mmHg and increase from baseline >=15 mmHg.

5. Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period [52 weeks]

   Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female adults aged ≥40 yrs

• Smoking history of at least 10 pack years

• Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008)

• Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%

Exclusion Criteria:

• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1

• Patients with concomitant pulmonary disease

• Patients with a history of asthma

• Any patient with lung cancer or a history of lung cancer

• Patients with a history of certain cardiovascular co-morbid conditions

• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency

• Patients in the active phase of a supervised pulmonary rehabilitation program

• Patients contraindicated for inhaled anticholinergic agents and β2 agonists

• Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Toronto	Ontario	Canada	M3H 5S4
2	Novartis Investigative Site	Mirabel	Quebec	Canada	J7J 2K8
3	Novartis Investigative Site	Québec	Quebec	Canada	G1G 3Z4
4	Novartis Investigative Site	Quebec		Canada	G1P 1J6
5	Novartis Investigative Site	Beuvry		France	62660
6	Novartis Investigative Site	Ferolles-Attily		France	77150
7	Novartis Investigative Site	Montpellier		France	34059
8	Novartis Investigative Site	Nantes		France	44000
9	Novartis Investigative Site	Pessac		France	33604
10	Novartis Investigative Site	Aszod		Hungary	2170
11	Novartis Investigative Site	Baja		Hungary	6500
12	Novartis Investigative Site	Erd		Hungary	2030
13	Novartis Investigative Site	Godollo		Hungary	2100
14	Novartis Investigative Site	Makó		Hungary	6900
15	Novartis Investigative Site	New Delhi	Delhi	India	110029
16	Novartis Investigative Site	Banglaore	Karnataka	India	560027
17	Novartis Investigative Site	Mysore	Karnataka	India	570004
18	Novartis Investigative Site	Indore	Madhya Pradesh	India	452001
19	Novartis Investigative Site	Mumbai	Maharashtra	India	400007
20	Novartis Investigative Site	Dehli	New Delhi	India	110063
21	Novartis Investigative Site	Coimbatore	Tamil Nadu	India	641044
22	Novartis Investigative Site	Chennai - Tamil Nadu		India	600 087
23	Novartis Investigative Site	Mangalore		India
24	Novartis Investigative Site	Koyang-si	Gyeonggi-do	Korea, Republic of	410-773
25	Novartis Investigative Site	Busan		Korea, Republic of	602-739
26	Novartis Investigative Site	Seoul		Korea, Republic of	140-743
27	Novartis Investigative Site	Seoul		Korea, Republic of	158-710
28	Novartis Investigative Site	Riga	LV	Latvia	LV-1038
29	Novartis Investigative Site	Daugavpils		Latvia	LV-5401
30	Novartis Investigative Site	Jekabpils		Latvia	LV-5201
31	Novartis Investigative Site	Riga		Latvia	1002
32	Novartis Investigative Site	Alytus		Lithuania	LT-62114
33	Novartis Investigative Site	Kaunas		Lithuania	44320
34	Novartis Investigative Site	Klaipeda		Lithuania	92288
35	Novartis Investigative Site	Klaipeda		Lithuania	LT-92231
36	Novartis Investigative Site	Vilnius		Lithuania	06001
37	Novartis Investigative Site	Vilnius		Lithuania	LT-08661
38	Novartis Investigative Site	Bucharest	District 1	Romania	011422
39	Novartis Investigative Site	Bucharest	District 1	Romania	10457
40	Novartis Investigative Site	Bucharest	District 3	Romania	030303
41	Novartis Investigative Site	Brasov	Jud. Brasov	Romania	500118
42	Novartis Investigative Site	Iasi	Jud. Iasi	Romania	700115
43	Novartis Investigative Site	Pretoria		South Africa	0184
44	Novartis Investigative Site	Pretoria		South Africa
45	Novartis Investigative Site	Bath		United Kingdom	BA1 2SR
46	Novartis Investigative Site	Bath		United Kingdom	BA2 3HT
47	Novartis Investigative Site	Cambridge		United Kingdom	CB7 5JD
48	Novartis Investigative Site	Chesterfield		United Kingdom	S40 4TF
49	Novartis Investigative Site	Glasgow		United Kingdom	G69 7AD
50	Novartis Investigative Site	Irvine		United Kingdom	KA12 0AY
51	Novartis Investigative Site	Lancashire		United Kingdom	FY3 7EN
52	Novartis Investigative Site	Watford		United Kingdom	WD25 0EA
53	Novartis Investigative Site	Wellingborough		United Kingdom	NN8 4RW

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01120717
• Other Study ID Numbers: CQVA149A2307; 2009-013235-38
• First Posted: May 11, 2010
• Last Update Posted: Jan 31, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Novartis Pharmaceuticals: QVA149; COPD; combination bronchodilator
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Pre-assignment Detail	Randomization ratio in the study was 2:1 for QVA149 and Placebo groups. Patients were not stratified by COPD disease severity.

Arm/Group Title	QVA149	Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Period Title: Overall Study
STARTED	226	113
Safety Population: Received Study Drug	225	113
COMPLETED	194	89
NOT COMPLETED	32	24

Baseline Characteristics

Arm/Group Title	QVA149	Placebo	Total
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI	Total of all reporting groups
Overall Participants	225	113	338
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (8.81)	62.9 (8.14)	62.6 (8.58)
Sex: Female, Male (Count of Participants)
Female	51 22.7%	27 23.9%	78 23.1%
Male	174 77.3%	86 76.1%	260 76.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events, Serious Adverse Events or Death
Description	Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Time Frame	52 weeks + Follow-up (Up to Day 394)

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with safety assessments were included in this analysis.

Arm/Group Title	QVA149	Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Measure Participants	225	113
Adverse events	130 57.8%	64 56.6%
Serious adverse events	37 16.4%	12 10.6%
Death - 1st treatment day to 30d after last dose	4 1.8%	1 0.9%
Death - last dose + 30d until end of follow-up	1 0.4%	0 0%

2. Secondary Outcome

Title	Pre-dose FEV1
Description	Pre-dose FEV1 is defined as the average of the FEV1 15 minutes pre-dose and FEV1 45 minutes pre-dose. A mixed model was used with treatment as a fixed effect, average of 15 min and 45 min pre-dose FEV1 at visit 3 as the baseline measurement, and FEV1 prior to inhalation and FEV1 60 min post inhalation of two short acting bronchodialators as covariates. The model also included smoking status at baseline, history of ICS use and country as fixed effects with center nested within country as a random effect.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomized patients who received at least one dose of study drug. Only patients with the required data were included in this analysis.

Arm/Group Title	QVA149	Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Measure Participants	191	88
Least Squares Mean (Standard Error) [Liter]	1.607 (0.0230)	1.418 (0.0297)

3. Secondary Outcome

Title	Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable hematology values were: hemoglobin - male <115g/L, female <95 g/L; hematocrit - male <0.37v/v, female <0.32v/v; white cell count - <2.8 10E9/L or >16.0 10E9/L; platelets - <75 10E9/L or >700 10E9/L
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with the required data were included in this analysis.

Arm/Group Title	QVA149	Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Measure Participants	225	113
Hemoglobin - male <115g/L (n = 164, 77)	9 4%	1 0.9%
Hemoglobin - female <95g/L (n = 50, 25)	0 0%	0 0%
Hematocrit - male <0.37v/v (n = 164, 77)	11 4.9%	3 2.7%
Hematocrit - female <0.32v/v (n = 49, 25)	0 0%	0 0%
WBC (total) - <2.8 10E9/L (n = 214, 102)	0 0%	0 0%
WBC (total) - >16.0 10E9/L (n = 214, 102)	0 0%	0 0%
Platelet count (direct) - <75 10E9/L (n = 214,102)	1 0.4%	0 0%
Platelet count (direct) - >700 10E9/L (n=214, 102)	0 0%	0 0%

4. Secondary Outcome

Title	Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable biochemistry values were: sodium <125mmol/L or >160mmol/L; potassium <3.0mmol/L or >6.0mmol/L; BUN >9.99mmol/L; creatinine >176.8µmol/L; total protein (serum) <40g/L or >95g/L; albumin <25g/L; bilirubin (total) >34.2µmol/L; SGPT >3 x ULN; SGOT > 3 x ULN; gamma glutamyltransferase >3 x ULN; alkaline phosphatase (serum) >3 x ULN; glucose <2.78mmol/L or >9.99mmol/L
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with the required data were included in this analysis.

Arm/Group Title	QVA149	Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Measure Participants	214	101
Sodium - <125mmol/L	0 0%	0 0%
Sodium - >160mmol/L	0 0%	0 0%
Potassium - <3.0mmol/L	0 0%	0 0%
Potassium - >6.0mmol/L	2 0.9%	1 0.9%
BUN - >9.99mmol/L	14 6.2%	4 3.5%
Creatinine - >176.8µmol/L	1 0.4%	1 0.9%
Total protein (serum) - <40g/L	0 0%	0 0%
Total protein (serum) - >95g/L	0 0%	0 0%
Albumin - <25g/L	0 0%	0 0%
Bilirubin (total) - >34.2µmol/L (n = 213, 101)	0 0%	0 0%
SGPT - >3 x ULN	2 0.9%	1 0.9%
SGOT - >3 x ULN	1 0.4%	2 1.8%
Gamma glutamyltransferase - >3 x ULN	8 3.6%	7 6.2%
Alkaline phosphatase, serum - >3 x ULN	0 0%	0 0%
Glucose - <2.78mmol/L	0 0%	0 0%
Glucose - >9.99mmol/L	16 7.1%	3 2.7%

5. Secondary Outcome

Title	Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable vital sign values were: pulse rate - low, <40 bpm or <=50 bpm and decrease from baseline >=15bpm; pulse rate high, >130 bpm or >=120bpm and increase from baseline >=15 bpm. Systolic blood pressure - low, <75 mmHg or <=90 mmHg and decrease from baseline >=20 mmHg; high, >200 mmHg or >=180 mmHg and increase from baseline >=20 mmHg. Diastolic blood pressure - low, <40 mmHg or <=50 mmHg and decrease from baseline >=15 mmHg; high, >115 mmHg or >=105 mmHg and increase from baseline >=15 mmHg.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with the required data were included in this analysis.

Arm/Group Title	QVA149	Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Measure Participants	225	113
Pulse rate - low	0 0%	1 0.9%
Pulse rate - high	0 0%	0 0%
Systolic blood pressure - low	0 0%	0 0%
Systolic blood pressure - high	3 1.3%	0 0%
Diastolic blood pressure - low	0 0%	3 2.7%
Diastolic blood pressure - high	2 0.9%	2 1.8%

6. Secondary Outcome

Title	Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period
Description	Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with the required data were included in this analysis.

Arm/Group Title	QVA149	Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Measure Participants	225	113
30 to 60ms change from baseline	7 3.1%	5 4.4%
> 60ms change from baseline	0 0%	1 0.9%

Adverse Events

Time Frame	Adverse Events were collected up to Day 394
Arm/Group Title	QVA149		Placebo
Arm/Group Description	110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)		Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
All Cause Mortality
	QVA149		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	QVA149		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/225 (16.4%)		12/113 (10.6%)
Blood and lymphatic system disorders
Anaemia	0/225 (0%)		1/113 (0.9%)
Cardiac disorders
Cardiac failure congestive	2/225 (0.9%)		0/113 (0%)
Cardio-respiratory arrest	1/225 (0.4%)		0/113 (0%)
Coronary artery disease	1/225 (0.4%)		0/113 (0%)
Myocardial ischaemia	1/225 (0.4%)		0/113 (0%)
Sinus tachycardia	1/225 (0.4%)		0/113 (0%)
Supraventricular tachycardia	1/225 (0.4%)		0/113 (0%)
Ear and labyrinth disorders
Vertigo	1/225 (0.4%)		0/113 (0%)
Vestibular disorder	0/225 (0%)		1/113 (0.9%)
Endocrine disorders
Autoimmune thyroiditis	1/225 (0.4%)		0/113 (0%)
Gastrointestinal disorders
Bezoar	1/225 (0.4%)		0/113 (0%)
Gastric ulcer	0/225 (0%)		1/113 (0.9%)
Gastric ulcer haemorrhage	0/225 (0%)		1/113 (0.9%)
Pancreatitis acute	1/225 (0.4%)		0/113 (0%)
Volvulus	0/225 (0%)		1/113 (0.9%)
Immune system disorders
Drug hypersensitivity	1/225 (0.4%)		0/113 (0%)
Infections and infestations
Lower respiratory tract infection	1/225 (0.4%)		0/113 (0%)
Pneumonia	8/225 (3.6%)		0/113 (0%)
Pulmonary tuberculosis	1/225 (0.4%)		0/113 (0%)
Respiratory tract infection viral	0/225 (0%)		1/113 (0.9%)
Upper respiratory tract infection	1/225 (0.4%)		1/113 (0.9%)
Upper respiratory tract infection bacterial	1/225 (0.4%)		0/113 (0%)
Urinary tract infection	1/225 (0.4%)		0/113 (0%)
Injury, poisoning and procedural complications
Contusion	1/225 (0.4%)		0/113 (0%)
Femoral neck fracture	1/225 (0.4%)		0/113 (0%)
Foot fracture	1/225 (0.4%)		0/113 (0%)
Hip fracture	1/225 (0.4%)		0/113 (0%)
Road traffic accident	0/225 (0%)		1/113 (0.9%)
Spinal compression fracture	0/225 (0%)		1/113 (0.9%)
Spinal fracture	1/225 (0.4%)		0/113 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	0/225 (0%)		1/113 (0.9%)
Basal cell carcinoma	1/225 (0.4%)		0/113 (0%)
Bladder cancer	1/225 (0.4%)		0/113 (0%)
Bladder neoplasm	1/225 (0.4%)		0/113 (0%)
Hepatic neoplasm malignant	0/225 (0%)		1/113 (0.9%)
Lung neoplasm	1/225 (0.4%)		0/113 (0%)
Lung neoplasm malignant	2/225 (0.9%)		1/113 (0.9%)
Metastases to central nervous system	1/225 (0.4%)		0/113 (0%)
Prostatic adenoma	1/225 (0.4%)		0/113 (0%)
Nervous system disorders
Intracranial pressure increased	1/225 (0.4%)		0/113 (0%)
Transient ischaemic attack	1/225 (0.4%)		0/113 (0%)
Renal and urinary disorders
Urinary retention	1/225 (0.4%)		0/113 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/225 (0.4%)		0/113 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	12/225 (5.3%)		4/113 (3.5%)
Lung disorder	0/225 (0%)		1/113 (0.9%)
Pneumothorax	1/225 (0.4%)		0/113 (0%)
Vascular disorders
Essential hypertension	1/225 (0.4%)		0/113 (0%)
Hypertension	1/225 (0.4%)		0/113 (0%)
Thrombosis	1/225 (0.4%)		0/113 (0%)
Other (Not Including Serious) Adverse Events
	QVA149		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/225 (36.4%)		41/113 (36.3%)
Infections and infestations
Lower respiratory tract infection	14/225 (6.2%)		4/113 (3.5%)
Upper respiratory tract infection	11/225 (4.9%)		8/113 (7.1%)
Viral upper respiratory tract infection	18/225 (8%)		15/113 (13.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	56/225 (24.9%)		27/113 (23.9%)
Cough	18/225 (8%)		7/113 (6.2%)
Vascular disorders
Hypertension	3/225 (1.3%)		6/113 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.