Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00393458
• Collaborator: (none)
• Enrollment: 1,732
• Locations: 183
• Arms: 4
• Duration (Months): 21
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study was designed to assess the efficacy and long-term safety of 300 and 600 µg doses of indacaterol when delivered via a single-dose dry-powder inhaler (SDDPI) in patients with chronic obstructive pulmonary disease (COPD). Patients were randomized to receive either indacaterol 300 µg once daily, indacaterol 600 µg once daily, formoterol 12 µg twice daily, or placebo.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Indacaterol; Drug: Formoterol; Drug: Placebo to indacaterol; Drug: Placebo to formoterol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1732 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 52-week Treatment, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol (300 and 600 µg Once Daily) in Patients With Chronic Obstructive Pulmonary Disease, Using Formoterol (12 µg Twice Daily) as an Active Control
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Indacaterol 300 μg plus placebo to formoterol Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to formoterol; Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).
Experimental: Indacaterol 600 μg plus placebo to formoterol Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to formoterol; Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).
Active Comparator: Formoterol 12 μg plus placebo to indacaterol Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Formoterol; Formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).; Drug: Placebo to indacaterol; Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
Placebo Comparator: Placebo to indacaterol plus placebo to formoterol Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Placebo to indacaterol; Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to formoterol; Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).

Outcome Measures

Primary Outcome Measures

1. Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85 [Week 12 + 1 day, Day 85]

   FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Secondary Outcome Measures

1. Percentage of Days of Poor Control During 52 Weeks of Treatment [Baseline to end of study (Week 52)]

   Percentage of days of poor control was defined as the number of days in the patient diary with a score ≥ 2 (scale of 0-3, a higher number means more severe symptoms) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness) over 52 weeks divided by the number of evaluable days (days with ≥ 2 symptoms with scores). The analysis included baseline percentage of days of poor control, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male and female adults ≥ 40 years, with a diagnosis of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2005 and:

1. Smoking history of at least 20 pack years

2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% of the predicted normal value

3. Post-bronchodilator FEV1/FVC (forced volume capacity) < 70% (Post refers to within 30 minutes after inhalation of 400 μg of salbutamol)

Exclusion Criteria:

• Patients who were hospitalized for a COPD exacerbation in the 6 weeks prior to screening.

• Patients who had a respiratory tract infection within 6 weeks prior to screening.

• Patients with concomitant pulmonary disease.

• Patients with a history of asthma.

• Patients with diabetes type I or uncontrolled diabetes type II.

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

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

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	Buenos Aires		Argentina
2	Novartis	Buenos Aires		Argentina
3	Novartis Investigator Site	Mendoza		Argentina
4	Novartis Investigator Site	San Miguel		Argentina
5	Novartis Investigator Site	Santa Fe		Argentina
6	Novartis Investigator Site	Rancagua		Chile
7	Novartis	Santiago		Chile
8	Novartis Investigator Site	Vina del Mar		Chile
9	Novartis Investigator Site	Barranquilla		Colombia
10	Novartis	Bogota		Colombia
11	Novartis Investigator Site	Medellin		Colombia
12	Novartis Investigator Site	Cvikov		Czech Republic
13	Novartis Investigator Site	Kyjov		Czech Republic
14	Novartis Investigator Site	Ostrava Poruba		Czech Republic
15	Novartis Investigator Site	Pardubice		Czech Republic
16	Novartis	Praha		Czech Republic
17	Novartis Investigator Site	Tabor		Czech Republic
18	Novartis Investigator Site	Zatec		Czech Republic
19	Novartis Investigator Site	Aarhus		Denmark
20	Novartis	Copenhagen		Denmark
21	Novartis Investigator Site	Hellerup		Denmark
22	Novartis Investigator Site	Hvidovre		Denmark
23	Novartis Investigator Site	Molleparkvej		Denmark
24	Novartis Investigator Site	Odense		Denmark
25	Novartis Investigator Site	Guayaquil		Ecuador
26	Novartis Investigator Site	Quito		Ecuador
27	Novartis	Quito		Ecuador
28	Novartis Investigator Site	Alexandria		Egypt
29	Novartis Investigator Site	Assiut		Egypt
30	Novartis Investigator Site	Cairo		Egypt
31	Novartis	Cairo		Egypt
32	Novartis Investigator Site	Tallinn		Estonia
33	Novartis	Tartu		Estonia
34	Novartis Investigator Site	Beuvry		France
35	Novartis Investigator Site	Chamalieres		France
36	Novartis Investigator Site	Ferolles-Attilly		France
37	Novartis Investigator Site	Grasse		France
38	Novartis Investigator Site	Marseilles		France
39	Novartis Investigator Site	Montpellier Cedex		France
40	Novartis Investigator Site	Nice		France
41	Novartis Investigator Site	Nimes		France
42	Novartis Investigator Site	Paris		France
43	Novartis Investigator Site	Perpignan		France
44	Novartis Investigator Site	Pessac Cedex		France
45	Novartis Investigator Site	Strasbourg		France
46	Novartis Investigator Site	Augsburg		Germany
47	Novartis Investigator Site	Bad Segeberg		Germany
48	Novartis Investigator Site	Bad Worishofen		Germany
49	Novartis Investigator Site	Berlin		Germany
50	Novartis Investigator Site	Bielefeld		Germany
51	Novartis Investigator Site	Bochum		Germany
52	Novartis Investigator Site	Bonn		Germany
53	Novartis Investigator Site	Borstel		Germany
54	Novartis Investigator Site	Darmstadt		Germany
55	Novartis Investigator Site	Dortmund		Germany
56	Novartis Investigator Site	Erfurt		Germany
57	Novartis Investigator Site	Forchheim		Germany
58	Novartis Investigator Site	Frankfurt		Germany
59	Novartis Investigator Site	Gauting		Germany
60	Novartis Investigator Site	Geesthacht		Germany
61	Novartis Investigator Site	Gelsenkirchen		Germany
62	Novartis Investigator Site	Grosshansdorf		Germany
63	Novartis Investigator Site	Gummersbach		Germany
64	Novartis Investigator Site	Hagen		Germany
65	Novartis Investigator Site	Hamburg		Germany
66	Novartis Investigator Site	Hannover		Germany
67	Novartis Investigator Site	Ilvesheim		Germany
68	Novartis Investigator Site	Kassel		Germany
69	Novartis Investigator Site	Kiel		Germany
70	Novartis Investigator Site	Leipzig		Germany
71	Novartis Investigator Site	Luebeck		Germany
72	Novartis Investigator Site	Luedenscheid		Germany
73	Novartis Investigator Site	Mainz		Germany
74	Novartis Investigator Site	Marburg		Germany
75	Novartis Investigator Site	Muenchen		Germany
76	Novartis Investigator Site	Neumunster		Germany
77	Novartis	Nürnberg		Germany
78	Novartis Investigator Site	Oschersleben		Germany
79	Novartis Investigator Site	Ruedersdorf		Germany
80	Novartis Investigator Site	Schoenefeld		Germany
81	Novartis Investigator Site	Strausberg		Germany
82	Novartis Investigator Site	Witten		Germany
83	Novartis Investigator Site	Wuppertal		Germany
84	Novartis Investigator Site	Budapest		Hungary
85	Novartis	Budapest		Hungary
86	Novartis Investigator Site	Deszk		Hungary
87	Novartis Investigator Site	Matrahaza		Hungary
88	Novartis Investigator Site	Mosdos		Hungary
89	Novartis Investigator Site	Sopron		Hungary
90	Novartis Investigator Site	Jerusalem		Israel
91	Novartis	Petach-Tikva		Israel
92	Novartis Investigator Site	Rehovot		Israel
93	Novartis Investigator Site	Tel-Hashomer		Israel
94	Novartis Investigator Site	Ancona		Italy
95	Novartis Investigator Site	Catania		Italy
96	Novartis Investigator Site	Ferrara		Italy
97	Novartis Investigator Site	Firenze		Italy
98	Novartis Investigator Site	Foggia		Italy
99	Novartis Investigator Site	Genova		Italy
100	Novartis Investigator Site	Milano		Italy
101	Novartis	Milano		Italy
102	Novartis Investigator Site	Pisa		Italy
103	Novartis Investigator Site	Roma		Italy
104	Novartis Investigator Site	Siena		Italy
105	Novartis Investigator Site	Kyunggi		Korea, Republic of
106	Novartis Investigator Site	Seoul		Korea, Republic of
107	Novartis	Seoul		Korea, Republic of
108	Novartis Investigator Site	Suwon		Korea, Republic of
109	Novartis Investigator Site	Uijeongbu-si		Korea, Republic of
110	Novartis Investigator Site	Daugavpils		Latvia
111	Novartis Investigator Site	Jekabpils		Latvia
112	Novartis Investigator Site	Riga		Latvia
113	Novartis	Riga		Latvia
114	Novartis Investigator Site	Alytus		Lithuania
115	Novartis Investigator Site	Kaunas		Lithuania
116	Novartis	Kaunas		Lithuania
117	Novartis Investigator Site	Klaipeda		Lithuania
118	Novartis Investigator Site	Vilnius		Lithuania
119	Novartis Investigator Site	Almelo		Netherlands
120	Novartis Investigator Site	Amersfoort		Netherlands
121	Novartis	Arnhem		Netherlands
122	Novartis Investigator Site	Breda		Netherlands
123	Novartis Investigator Site	Ede		Netherlands
124	Novartis Investigator Site	Eindhoven		Netherlands
125	Novartis Investigator Site	Harderwijk		Netherlands
126	Novartis Investigator Site	Helmond		Netherlands
127	Novartis Investigator Site	Hengelo		Netherlands
128	Novartis Investigator Site	Hoorn		Netherlands
129	Novartis Investigator Site	Leeuwarden		Netherlands
130	Novartis Investigator Site	Rotterdam		Netherlands
131	Novartis Investigator Site	Sneek		Netherlands
132	Novartis Investigator Site	Veldhoven		Netherlands
133	Novartis Investigator Site	Zutphen		Netherlands
134	Novartis Investigator Site	Lima		Peru
135	Novartis	Lima		Peru
136	Novartis	Bucharest		Romania
137	Novartis Investigator Site	Cluj-Napoca		Romania
138	Novartis Investigator Site	Iasi		Romania
139	Novartis Investigator Site	Timisoara		Romania
140	Novartis Investigator Site	Kazan		Russian Federation
141	Novartis Investigator Site	Moscow		Russian Federation
142	Novartis	Moscow		Russian Federation
143	Novartis Investigator Site	Samara		Russian Federation
144	Novartis Investigator Site	St Petersburg		Russian Federation
145	Novartis Investigator Site	Yekaterinburg		Russian Federation
146	Novartis Investigator Site	Banska Bystrica		Slovakia
147	Novartis Investigator Site	Bratislava		Slovakia
148	Novartis	Bratislava		Slovakia
149	Novartis Investigator Site	Kosice		Slovakia
150	Novartis Investigator Site	Partizanske		Slovakia
151	Novartis Investigator Site	Alicante		Spain
152	Novartis Investigator Site	Barcelona		Spain
153	Novartis	Barcelona		Spain
154	Novartis Investigator Site	Begonte		Spain
155	Novartis Investigator Site	Caceres		Spain
156	Novartis Investigative Site	Madrid		Spain
157	Novartis Investigator Site	Mataro		Spain
158	Novartis Investigator Site	Petrel		Spain
159	Novartis Investigator Site	Ponferrada		Spain
160	Novartis Investigator Site	Terrassa		Spain
161	Novartis Investigator Site	Valencia		Spain
162	Novartis Investigator Site	Aarau		Switzerland
163	Novartis Investigator Site	Basel		Switzerland
164	Novartis Investigator Site	Locarno		Switzerland
165	Novartis Investigator Site	Munchenstein		Switzerland
166	Novartis Investigator Site	Zuerich		Switzerland
167	Novartis Investigator Site	Ankara		Turkey
168	Novartis Investigator Site	Bursa		Turkey
169	Novartis	Istanbul		Turkey
170	Novartis Investigator Site	Izmir		Turkey
171	Novartis Investigator Site	Mersin		Turkey
172	Novartis Investigator Site	Yenisehir		Turkey
173	Novartis Investigator Site	Belfast		United Kingdom
174	Novartis Investigator Site	Bexhill-on-Sea		United Kingdom
175	Novartis Investigator Site	Blackpool		United Kingdom
176	Novartis Investigator Site	Chertsey		United Kingdom
177	Novartis Investigator Site	Glasgow		United Kingdom
178	Novartis Investigator Site	Leicester		United Kingdom
179	Novartis Investigator Site	London		United Kingdom
180	Novartis Investigator Site	Manchester		United Kingdom
181	Novartis Investigator Site	Newcastle-upon-Tyne		United Kingdom
182	Novartis Investigator Site	Slough		United Kingdom
183	Novartis Investigator Site	Swansea		United Kingdom

Sponsors and Collaborators

• Novartis

Investigators

• Principal Investigator: Novartis Investigator Site, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00393458
• Other Study ID Numbers: CQAB149B2334
• First Posted: Oct 27, 2006
• Last Update Posted: Aug 18, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: chronic obstructive pulmonary disease; COPD; indacaterol; long-acting β2 agonist
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Formoterol Fumarate

Study Results

Participant Flow

Arm/Group Title	Indacaterol 300 μg Plus Placebo to Formoterol	Indacaterol 600 μg Plus Placebo to Formoterol	Formoterol 12 μg Plus Placebo to Indacaterol	Placebo to Indacaterol Plus Placebo to Formoterol
Arm/Group Description	Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Period Title: Overall Study
STARTED	437	428	435	432
Exposed to Study Medication or Placebo	437	425	434	432
COMPLETED	338	326	323	295
NOT COMPLETED	99	102	112	137

Baseline Characteristics

Arm/Group Title	Indacaterol 300 μg Plus Placebo to Formoterol	Indacaterol 600 μg Plus Placebo to Formoterol	Formoterol 12 μg Plus Placebo to Indacaterol	Placebo to Indacaterol Plus Placebo to Formoterol	Total
Arm/Group Description	Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Total of all reporting groups
Overall Participants	437	425	434	432	1728
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (8.57)	62.9 (8.74)	63.6 (8.49)	63.2 (8.28)	63.4 (8.52)
Sex: Female, Male (Count of Participants)
Female	86 19.7%	98 23.1%	86 19.8%	80 18.5%	350 20.3%
Male	351 80.3%	327 76.9%	348 80.2%	352 81.5%	1378 79.7%

Outcome Measures

1. Primary Outcome

Title	Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85
Description	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Time Frame	Week 12 + 1 day, Day 85

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug, excluding patients from a number of centers.

Arm/Group Title	Indacaterol 300 μg Plus Placebo to Formoterol	Indacaterol 600 μg Plus Placebo to Formoterol	Formoterol 12 μg Plus Placebo to Indacaterol	Placebo to Indacaterol Plus Placebo to Formoterol
Arm/Group Description	Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Measure Participants	389	374	379	371
Least Squares Mean (Standard Error) [Liters]	1.48 (0.012)	1.48 (0.013)	1.38 (0.013)	1.31 (0.013)

2. Secondary Outcome

Title	Percentage of Days of Poor Control During 52 Weeks of Treatment
Description	Percentage of days of poor control was defined as the number of days in the patient diary with a score ≥ 2 (scale of 0-3, a higher number means more severe symptoms) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness) over 52 weeks divided by the number of evaluable days (days with ≥ 2 symptoms with scores). The analysis included baseline percentage of days of poor control, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Time Frame	Baseline to end of study (Week 52)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug, excluding patients from a number of centers.

Arm/Group Title	Indacaterol 300 μg Plus Placebo to Formoterol	Indacaterol 600 μg Plus Placebo to Formoterol	Formoterol 12 μg Plus Placebo to Indacaterol	Placebo to Indacaterol Plus Placebo to Formoterol
Arm/Group Description	Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Measure Participants	386	370	377	366
Least Squares Mean (Standard Error) [Percentage of days]	33.6 (1.43)	30.0 (1.46)	33.5 (1.45)	38.3 (1.47)

Adverse Events

Time Frame	Safety population: All patients who received at least 1 dose of study drug.
Adverse Event Reporting Description	Baseline to the end of the study (Week 52)
Arm/Group Title	Indacaterol 300 μg Plus Placebo to Formoterol		Indacaterol 600 μg Plus Placebo to Formoterol		Formoterol 12 μg Plus Placebo to Indacaterol		Placebo to Indacaterol Plus Placebo to Formoterol
Arm/Group Description	Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.		Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.		Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.		Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
All Cause Mortality
	Indacaterol 300 μg Plus Placebo to Formoterol		Indacaterol 600 μg Plus Placebo to Formoterol		Formoterol 12 μg Plus Placebo to Indacaterol		Placebo to Indacaterol Plus Placebo to Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol 300 μg Plus Placebo to Formoterol		Indacaterol 600 μg Plus Placebo to Formoterol		Formoterol 12 μg Plus Placebo to Indacaterol		Placebo to Indacaterol Plus Placebo to Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/437 (14.4%)		51/425 (12%)		69/434 (15.9%)		48/432 (11.1%)
Blood and lymphatic system disorders
Anaemia	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Cardiac disorders
Acute myocardial infarction	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Angina pectoris	1/437 (0.2%)		1/425 (0.2%)		0/434 (0%)		1/432 (0.2%)
Angina unstable	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Atrial fibrillation	3/437 (0.7%)		0/425 (0%)		1/434 (0.2%)		1/432 (0.2%)
Atrial flutter	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		1/432 (0.2%)
Atrial tachycardia	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Atrioventricular block	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Cardiac arrest	0/437 (0%)		0/425 (0%)		0/434 (0%)		2/432 (0.5%)
Cardiac failure	1/437 (0.2%)		1/425 (0.2%)		1/434 (0.2%)		0/432 (0%)
Cardiac failure congestive	2/437 (0.5%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Cardiomyopathy	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Coronary artery disease	0/437 (0%)		3/425 (0.7%)		0/434 (0%)		0/432 (0%)
Ischaemic cardiomyopathy	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Microvascular angina	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Myocardial infarction	1/437 (0.2%)		2/425 (0.5%)		1/434 (0.2%)		1/432 (0.2%)
Myocardial ischaemia	2/437 (0.5%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Palpitations	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Pericarditis	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Sinus arrhythmia	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Sinus bradycardia	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Stress cardiomyopathy	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Ear and labyrinth disorders
Vertigo	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Eye disorders
Anterior capsule contraction	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Cataract	2/437 (0.5%)		0/425 (0%)		2/434 (0.5%)		1/432 (0.2%)
Macular degeneration	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Retinal artery occlusion	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Appendicitis perforated	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Colonic polyp	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Duodenal ulcer	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Femoral hernia	1/437 (0.2%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Gastric haemorrhage	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Gastric ulcer	0/437 (0%)		1/425 (0.2%)		1/434 (0.2%)		0/432 (0%)
Gastric ulcer haemorrhage	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Gastrointestinal haemorrhage	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		1/432 (0.2%)
Gastrointestinal necrosis	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Inguinal hernia	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		2/432 (0.5%)
Mallory-Weiss syndrome	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Pancreatitis	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Pancreatitis acute	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Swollen tongue	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
General disorders
Chest pain	1/437 (0.2%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Hyperthermia	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Non-cardiac chest pain	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Sudden death	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		3/432 (0.7%)
Hepatobiliary disorders
Cholecystitis acute	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Cholelithiasis	1/437 (0.2%)		0/425 (0%)		1/434 (0.2%)		2/432 (0.5%)
Hepatitis alcoholic	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Immune system disorders
Contrast media allergy	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Infections and infestations
Appendicitis	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Bronchitis	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Erysipelas	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Gastroenteritis	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Lower respiratory tract infection	2/437 (0.5%)		2/425 (0.5%)		5/434 (1.2%)		3/432 (0.7%)
Lower respiratory tract infection bacterial	1/437 (0.2%)		0/425 (0%)		2/434 (0.5%)		0/432 (0%)
Nasopharyngitis	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Otitis media chronic	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Perianal abscess	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Pneumonia	3/437 (0.7%)		2/425 (0.5%)		5/434 (1.2%)		2/432 (0.5%)
Postoperative wound infection	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Pulmonary tuberculosis	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Pyothorax	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Respiratory tract infection	0/437 (0%)		1/425 (0.2%)		2/434 (0.5%)		0/432 (0%)
Septic shock	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Upper respiratory tract infection	0/437 (0%)		0/425 (0%)		3/434 (0.7%)		0/432 (0%)
Upper respiratory tract infection bacterial	4/437 (0.9%)		0/425 (0%)		5/434 (1.2%)		4/432 (0.9%)
Viral infection	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Viral upper respiratory tract infection	1/437 (0.2%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Injury, poisoning and procedural complications
Cardiac procedure complication	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Clavicle fracture	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Femoral neck fracture	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Foot fracture	0/437 (0%)		2/425 (0.5%)		0/434 (0%)		1/432 (0.2%)
Hip fracture	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Humerus fracture	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Lower limb fracture	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Multiple fractures	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Pneumothorax traumatic	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Rib fracture	2/437 (0.5%)		1/425 (0.2%)		1/434 (0.2%)		0/432 (0%)
Road traffic accident	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Tendon rupture	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Upper limb fracture	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Wrist fracture	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Investigations
Blood creatine increased	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Blood urea increased	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Colonoscopy	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Electrocardiogram QT prolonged	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Laboratory test abnormal	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Hypokalaemia	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Intervertebral disc protrusion	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Osteoarthritis	1/437 (0.2%)		0/425 (0%)		1/434 (0.2%)		1/432 (0.2%)
Osteochondrosis	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Rheumatoid arthritis	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Rotator cuff syndrome	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Benign neoplasm of bladder	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Benign soft tissue neoplasm	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Bladder papilloma	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Breast cancer	0/437 (0%)		1/425 (0.2%)		1/434 (0.2%)		0/432 (0%)
Bronchial carcinoma	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Carcinoid tumour of the small bowel	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Cervix carcinoma stage 0	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Colon cancer	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Gastric cancer	0/437 (0%)		0/425 (0%)		0/434 (0%)		2/432 (0.5%)
Laryngeal cancer	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Laryngeal neoplasm	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Lung neoplasm malignant	0/437 (0%)		1/425 (0.2%)		1/434 (0.2%)		1/432 (0.2%)
Metastases to bone	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Non-small cell lung cancer stage I	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Oesophageal carcinoma	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Pancreatic carcinoma	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Papilloma	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Prostate cancer	2/437 (0.5%)		1/425 (0.2%)		1/434 (0.2%)		0/432 (0%)
Rectal cancer	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Skin cancer	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Tracheal cancer	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Nervous system disorders
Brain injury	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Carotid artery stenosis	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Cerebral infarction	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Cerebral ischaemia	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Cerebrovascular accident	0/437 (0%)		1/425 (0.2%)		1/434 (0.2%)		0/432 (0%)
Convulsion	0/437 (0%)		0/425 (0%)		2/434 (0.5%)		0/432 (0%)
Facial palsy	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Grand mal convulsion	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Loss of consciousness	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Presyncope	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Syncope	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Vertebrobasilar insufficiency	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Psychiatric disorders
Alcohol withdrawal syndrome	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Anxiety	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Depression	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Renal and urinary disorders
Nephrolithiasis	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Proteinuria	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Renal colic	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Renal failure acute	1/437 (0.2%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Urinary incontinence	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		2/432 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Apnoea	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Bronchospasm	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Chronic obstructive pulmonary disease	18/437 (4.1%)		12/425 (2.8%)		32/434 (7.4%)		20/432 (4.6%)
Dyspnoea	3/437 (0.7%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Emphysema	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Epistaxis	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Hypercapnia	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Lung infiltration	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Obliterative bronchiolitis	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Pneumothorax	1/437 (0.2%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Productive cough	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		0/432 (0%)
Pulmonary embolism	1/437 (0.2%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Respiratory arrest	0/437 (0%)		0/425 (0%)		0/434 (0%)		2/432 (0.5%)
Respiratory failure	3/437 (0.7%)		0/425 (0%)		5/434 (1.2%)		1/432 (0.2%)
Surgical and medical procedures
Haemorrhoid operation	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Vascular disorders
Aortic aneurysm	2/437 (0.5%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Aortic aneurysm rupture	0/437 (0%)		0/425 (0%)		0/434 (0%)		1/432 (0.2%)
Arterial occlusive disease	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Arteriosclerosis obliterans	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Femoral artery occlusion	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Hypertension	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Hypertensive crisis	0/437 (0%)		0/425 (0%)		2/434 (0.5%)		0/432 (0%)
Iliac artery occlusion	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Peripheral ischaemia	0/437 (0%)		1/425 (0.2%)		0/434 (0%)		0/432 (0%)
Shock	0/437 (0%)		0/425 (0%)		1/434 (0.2%)		0/432 (0%)
Other (Not Including Serious) Adverse Events
	Indacaterol 300 μg Plus Placebo to Formoterol		Indacaterol 600 μg Plus Placebo to Formoterol		Formoterol 12 μg Plus Placebo to Indacaterol		Placebo to Indacaterol Plus Placebo to Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	199/437 (45.5%)		183/425 (43.1%)		164/434 (37.8%)		176/432 (40.7%)
Infections and infestations
Lower respiratory tract infection	25/437 (5.7%)		21/425 (4.9%)		17/434 (3.9%)		20/432 (4.6%)
Nasopharyngitis	73/437 (16.7%)		80/425 (18.8%)		62/434 (14.3%)		56/432 (13%)
Upper respiratory tract infection bacterial	26/437 (5.9%)		25/425 (5.9%)		20/434 (4.6%)		33/432 (7.6%)
Musculoskeletal and connective tissue disorders
Muscle spasms	23/437 (5.3%)		25/425 (5.9%)		12/434 (2.8%)		6/432 (1.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	128/437 (29.3%)		108/425 (25.4%)		112/434 (25.8%)		138/432 (31.9%)
Cough	32/437 (7.3%)		27/425 (6.4%)		17/434 (3.9%)		19/432 (4.4%)

Limitations/Caveats

[Not Specified]

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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 (ie, data from all sites) in the clinical trial.