Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Using Salmeterol as Active Control

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00567996
• Collaborator: (none)
• Enrollment: 1,002
• Locations: 130
• Arms: 3
• Patients Per Site: 7.7

Study Details

Study Description

Brief Summary

This study evaluated the safety and efficacy of 26 weeks treatment with indacaterol, placebo or salmeterol in patients with chronic obstructive pulmonary disease.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: Indacaterol 150 μg; Drug: Salmeterol 50 μg; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1002 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 26-week Treatment, Multi-center, Randomized, Double-blind, Double- Dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, and Safety of Indacaterol (150 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease, Using Salmeterol (50 µg b.i.d.) as an Active Control
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Indacaterol 150 μg Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol 150 μg; Indacaterol 150 μg once daily (o.d) inhaled; Drug: Placebo to Salmeterol; Placebo to salmeterol delivered via a proprietary dry powder inhaler
Placebo Comparator: Placebo Placebo to Indacaterol once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Placebo to Indacaterol; Placebo to Indacaterol inhaled via SDDPI.; Drug: Placebo to Salmeterol; Placebo to salmeterol delivered via a proprietary dry powder inhaler
Active Comparator: Salmeterol 50 μg Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Salmeterol 50 μg; Salmeterol 50 μg twice daily (b.i.d) delivered via a proprietary dry powder inhaler; Drug: Placebo to Indacaterol; Placebo to Indacaterol inhaled via SDDPI.

Outcome Measures

Primary Outcome Measures

1. Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment [Week 12]

   Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.

Secondary Outcome Measures

1. St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment [Week 12]

   SGRQ is a health related quality of life questionnaire consisting of 76 items in three sections: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health status. The mixed model used baseline SGRQ total score, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.

2. Percentage of COPD "Days of Poor Control" During 26 Weeks of Treatment [Up to 26 weeks]

   Participants rated their symptoms on a scale of 0=none to 3=severe. A Chronic Obstructive Pulmonary Disease (COPD) "day of poor control" was defined as any day in the participants diary with a score >=2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). The mixed model used baseline percentage of "days of poor control", FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Clinical diagnosis of moderate to severe Chronic Obstructive Pulmonary Disease (COPD) as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006 Guidelines (mandatory) and including:

• Smoking history of at least 20 pack years

• Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% predicted and

or= 30% of predicted normal value

• Post-bronchodilator FEV1/FVC < 70%

("Post" defined as within 30 minutes of inhalation of 400 µg salbutamol)

Exclusion Criteria:

• Pregnant or nursing (lactating) women and women of child-bearing potential UNLESS they meet pre-specified definitions of post-menopausal or are using pre-specified acceptable methods of contraception

• Hospitalisation for COPD exacerbation in the 6 weeks prior to Visit 1 or during run-in

• Patients requiring oxygen therapy for chronic hypoxemia (typically >15h/day)

• Respiratory tract infection within 6 weeks prior to Visit 1 and during the run-in period

• Concomitant pulmonary disease

• Asthma history (eosinophils > 400/mm3; symptoms prior to age 40). Includes history of childhood asthma

• History of long QTc syndrome or QTc interval > 450 ms for males and >470 ms for females

• Patients who have a clinically significant condition or a clinically relevant laboratory abnormality

• History of reactions to sympathomimetic amines or inhaled medication

• Inability to use the dry powder devices or perform spirometry

• Irregular day/night, wake/sleep cycles, e.g. shift workers

• Certain medications for COPD and allied conditions such as long acting bronchodilators must not be used prior to Visit 1 and for a pre-specified minimum washout period

• Patients unable or unwilling to complete a patient diary

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Edmonton		Canada
2	Novartis Investigator Site	Edmonton		Canada
3	Novartis Investigator Site	London		Canada
4	Novartis Investigator Site	Mirabel		Canada
5	Novartis Investigator Site	Montreal		Canada
6	Novartis Investigator Site	Toronto		Canada
7	Novartis Investigator site	Barranquilla		Colombia
8	Novartis Investigator Site	Bogota D.C.		Colombia
9	Novartis Investigator Site	Medellin		Colombia
10	Novartis Investigator Site	Cvikov		Czech Republic
11	Novartis Investigator Site	Lovosice		Czech Republic
12	novartis Investigator site	Novy Jocin		Czech Republic
13	Novartis Investigator Site	Pardubice		Czech Republic
14	Novartis Investigator Site	Praha		Czech Republic
15	Novartis Investigative Site	Zatec		Czech Republic
16	Novartis Investigator Site	Aalborg		Denmark
17	Novartis Investigator Site	Arhus		Denmark
18	Novartis Investigative Site	Copenhagen		Denmark
19	Novartis Investigator Site	Copenhagen		Denmark
20	Novartis Investigator Site	Frederikssund		Denmark
21	Novartis investigator site	Hellerup		Denmark
22	Novartis Investigator site	Hvidovre		Denmark
23	Novartis investigator site	Odense		Denmark
24	Novartis Investigator Site	Roslev		Denmark
25	Novartis Investigative Site	Silkeborg		Denmark
26	Novartis Investgative Site	Soborg		Denmark
27	Novartis Investigator Site	Vaerloese		Denmark
28	Novartis Investigator Site	Hus		Finland
29	Novartis Investigator Site	Jyvaskyla		Finland
30	Novartis Investigator Site	Lahti		Finland
31	Novartis Investigator Site	Oulu		Finland
32	Novartis Investigator Site	Tampere		Finland
33	Novartis Investigator Site	Turku		Finland
34	Novartis Investigative Site	Ambroise		France
35	Novartis Investigative Site	Beuvry		France
36	Novartis Investgative Site	Ferolles-Attilly		France
37	Novartis Investigator Site	Nice		France
38	Novartis Investigator Site	Bad Segeberg		Germany
39	Novartis Investigator Site	Berlin		Germany
40	Novartis Investigator Site	Bielefeld		Germany
41	Novartis Investigator Site	Bochum		Germany
42	Novartis Investigator Site	Bonn		Germany
43	Novartis Investigator Site	Bruehl		Germany
44	Novartis Investigator Site	Cottbus		Germany
45	Novartis Investigator Site	Dortmund		Germany
46	Novartis Investigator Site	Dueren		Germany
47	Novartis Investigator Site	Eggenfelden		Germany
48	Novartis investigator site	Eschwege		Germany
49	Novartis Investigator Site	Forchheim		Germany
50	Novartis Investigator Site	Freudenberg		Germany
51	Novartis Investigator Site	Furth		Germany
52	Novartis Investigator Site	Gelsenkirchen		Germany
53	Novartis Investigator Site	Gummersbach		Germany
54	Novartis Investigator Site	Hagen		Germany
55	Novartis Investigator Site	Hannover		Germany
56	Novartis Investigator Site	Kassel		Germany
57	Novartis Investigator Site	Kempten		Germany
58	Novartis Investigator Site	Koeln		Germany
59	Novartis Investigator Site	Landsberg am Lech		Germany
60	Novartis Investigator Site	Langenfeld		Germany
61	Novartis Investigator Site	Leipzig		Germany
62	Novartis Investigator Site	Mainz		Germany
63	Novartis Investigator Site	Muenchen		Germany
64	Novartis Investigator Site	Munich		Germany
65	Novartis Investigator Site	Neuss		Germany
66	Novartis Investigator Site	Nuremburg		Germany
67	Novartis Investigator Site	Oschersleben		Germany
68	Novartis Investigator Site	Ruhmannsfelden		Germany
69	Novartis Investigator site	Sinsheim		Germany
70	Novartis Investigator Site	Solingen		Germany
71	Novartis Investigator Site	Steinfort-borghorst		Germany
72	Novartis Investigator Site	Vilshofen		Germany
73	Novartis Investigator Site	Wallerfing		Germany
74	Novartis Investigator Site	Witten		Germany
75	Novartis Investigator Site	Budapest		Hungary
76	Novartis investigator site	Debrechen		Hungary
77	Novartis Investigator Site	Deszk		Hungary
78	Novartis Investigator Site	Mosonmagyarovar		Hungary
79	Novartis Investigator Site	Szekesfehervar		Hungary
80	Novartis investigator site	Reykhavik		Iceland
81	Novartis Investigator Site	Chennai		India
82	Novartis Investigator Site	Coimbatore		India
83	Novartis Investigator Site	Goa		India
84	Novartis Investigator Site	Hyderabad		India
85	Novartis Investigator Site	Jaipur		India
86	Novartis Investigator Site	Kerala		India
87	Novartis Investigator Site	Mangalore		India
88	Novartis Investigator Site	Mumbai		India
89	Novartis Investigator Site	Vellore		India
90	Novartis Investigator Site	Ancona		Italy
91	Novartis Investigator Site	Arenzano		Italy
92	Novartis Investigative Site	Ascoli Piceno		Italy
93	Novartis Investigator Site	Brescia		Italy
94	Novartis Investigator Site	Cagliari		Italy
95	Novartis investigator site	Chieti		Italy
96	Novartis Investigator Site	Ferrara		Italy
97	Novartis Investigator Site	Milano		Italy
98	Novartis Investigator Site	Milan		Italy
99	Novartis Investigator Site	Orbassano		Italy
100	Novartis Investigator Site	Palermo		Italy
101	Novartis Investigator Site	Reggio Emilia		Italy
102	Novartis Investigator Site	Rome		Italy
103	Novartis Investigator Site	Sesto		Italy
104	Novartis Investigator Site	Siena		Italy
105	Novartis Investigator Site	Terni		Italy
106	Novartis Investigator Site	Callao		Peru
107	Novartis Investigator Site	Miraflores		Peru
108	Novartis Investigator Site	San Borja		Peru
109	Novartis Investigator Site	San Isidro		Peru
110	Novartis Investigator Site	San Martin de Porres		Peru
111	Novartis Investigator Site	Surco		Peru
112	Novartis Investigator Site	Ekaterinburg		Russian Federation
113	Novartis Investigator Site	Kazan		Russian Federation
114	Novartis Investigator Site	Moscow		Russian Federation
115	Novartis Investigator Site	Saint Petersburg		Russian Federation
116	Novartis Investigator Site	Samara		Russian Federation
117	Novartis Investigator Site	St Petersburg		Russian Federation
118	Novartis Investigator Site	Yaroslavl		Russian Federation
119	Novartis Investigator Site	Yekaterinburg		Russian Federation
120	Novartis Investigator Site	Bardejov		Slovakia
121	Novartis Investigator Site	Bratislava		Slovakia
122	Novartis Investigator Site	Kosice		Slovakia
123	Novartis Investigator Site	Kovice		Slovakia
124	Novartis Investigator Site	Spisska		Slovakia
125	Novartis Investigator Site	Changhua		Taiwan
126	Novartis Investigator Site	Kaohsiung		Taiwan
127	Novartis Investigator Site	Kaohusing		Taiwan
128	Novartis Investigator Site	Lin-ko		Taiwan
129	Novartis Investigator Site	Taichung		Taiwan
130	Novartis Investigator Site	Taipei		Taiwan

Sponsors and Collaborators

• Novartis

Investigators

• Study Chair: Novartis Pharma AG, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00567996
• Other Study ID Numbers: CQAB149B2336
• First Posted: Dec 5, 2007
• Last Update Posted: Aug 18, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: Chronic obstructive pulmonary disease, indacaterol, salmeterol, placebo controlled
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Study Results

Participant Flow

Pre-assignment Detail	1002 participants were randomized. 3 randomized participants in the Indacaterol group and 1 randomized participant in the Salmeterol group did not receive study medication and were not included in the intent-to-treat milestone.

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg	Placebo
Arm/Group Description	Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Period Title: Overall Study
STARTED	333	334	335
Intent-to-treat: Received Study Drug	330	333	335
COMPLETED	289	284	265
NOT COMPLETED	44	50	70

Baseline Characteristics

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg	Placebo	Total
Arm/Group Description	Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Total of all reporting groups
Overall Participants	330	333	335	998
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (8.67)	63.4 (9.19)	63.9 (8.56)	63.5 (8.81)
Sex: Female, Male (Count of Participants)
Female	92 27.9%	84 25.2%	77 23%	253 25.4%
Male	238 72.1%	249 74.8%	258 77%	745 74.6%

Outcome Measures

1. Primary Outcome

Title	Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment
Description	Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants who received at least one dose of study medication. The end point was analyzed only for those participants who had Trough FEV1 data at week 12. Missing data were imputed using Last Observation carried Forward (LOCF).

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg	Placebo
Arm/Group Description	Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Measure Participants	320	317	316
Least Squares Mean (Standard Error) [Liters]	1.45 (0.018)	1.39 (0.018)	1.28 (0.019)

2. Secondary Outcome

Title	St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment
Description	SGRQ is a health related quality of life questionnaire consisting of 76 items in three sections: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health status. The mixed model used baseline SGRQ total score, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants who received at least one dose of study medication. The endpoint was analyzed only for those participants who had SGRQ data at week 12. Missing data were imputed using Last Observation carried Forward (LOCF).

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg	Placebo
Arm/Group Description	Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Measure Participants	309	301	294
Least Squares Mean (Standard Error) [Score on a scale]	36.4 (1.04)	38.5 (1.04)	42.6 (1.05)

3. Secondary Outcome

Title	Percentage of COPD "Days of Poor Control" During 26 Weeks of Treatment
Description	Participants rated their symptoms on a scale of 0=none to 3=severe. A Chronic Obstructive Pulmonary Disease (COPD) "day of poor control" was defined as any day in the participants diary with a score >=2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). The mixed model used baseline percentage of "days of poor control", FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.
Time Frame	Up to 26 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants who received at least one dose of study medication. The endpoint was analyzed only for those participants who had data for this outcome measure.

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg	Placebo
Arm/Group Description	Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Measure Participants	310	310	304
Least Squares Mean (Standard Error) [Percentage of days]	34.1 (1.82)	34.1 (1.82)	38.1 (1.85)

Adverse Events

Time Frame	26 weeks
Adverse Event Reporting Description	Safety population consisting of all participants who received at least one dose of study medication.
Arm/Group Title	Indacaterol 150 μg		Salmeterol 50 μg		Placebo
Arm/Group Description	Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.		Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.		Placebo to Indacaterol once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
All Cause Mortality
	Indacaterol 150 μg		Salmeterol 50 μg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol 150 μg		Salmeterol 50 μg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/330 (8.8%)		19/333 (5.7%)		26/335 (7.8%)
Blood and lymphatic system disorders
Anaemia	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Cardiac disorders
Acute myocardial infarction	1/330 (0.3%)		1/333 (0.3%)		0/335 (0%)
Angina pectoris	1/330 (0.3%)		1/333 (0.3%)		0/335 (0%)
Atrial fibrillation	0/330 (0%)		1/333 (0.3%)		1/335 (0.3%)
Bundle branch block left	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Cardiac arrest	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Cardio-respiratory arrest	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Cor pulmonale acute	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Coronary artery disease	0/330 (0%)		2/333 (0.6%)		0/335 (0%)
Myocardial infarction	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Sick sinus syndrome	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Tricuspid valve incompetence	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Ear and labyrinth disorders
Vertigo	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Endocrine disorders
Goitre	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Gastrointestinal disorders
Abdominal pain	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Duodenal ulcer	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Gastric ulcer	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Gastritis	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Inguinal hernia	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Nausea	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Pancreatitis	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Rectal haemorrhage	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
General disorders
Multi-organ failure	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Hepatobiliary disorders
Cholelithiasis	2/330 (0.6%)		0/333 (0%)		0/335 (0%)
Infections and infestations
Cellulitis	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Diverticulitis	0/330 (0%)		0/333 (0%)		2/335 (0.6%)
Gastroenteritis	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Lower respiratory tract infection	2/330 (0.6%)		2/333 (0.6%)		2/335 (0.6%)
Pneumonia	0/330 (0%)		3/333 (0.9%)		0/335 (0%)
Sepsis	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Sinusitis	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Upper respiratory tract infection bacterial	2/330 (0.6%)		2/333 (0.6%)		0/335 (0%)
Viral infection	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Viral upper respiratory tract infection	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Subdural haemorrhage	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Traumatic intracranial haemorrhage	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/330 (0.3%)		0/333 (0%)		1/335 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Bladder cancer	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Diffuse large B-cell lymphoma	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Rectal cancer	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Nervous system disorders
Brachial plexopathy	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Cerebral infarction	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Cerebrovascular accident	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Epilepsy	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Hemiparesis	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Ischaemic stroke	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Transient ischaemic attack	0/330 (0%)		0/333 (0%)		2/335 (0.6%)
Psychiatric disorders
Alcoholism	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Renal and urinary disorders
Nephrolithiasis	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Renal failure chronic	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Reproductive system and breast disorders
Menorrhagia	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Ovarian cyst	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Acute respiratory failure	0/330 (0%)		0/333 (0%)		1/335 (0.3%)
Chronic obstructive pulmonary disease	8/330 (2.4%)		4/333 (1.2%)		10/335 (3%)
Dyspnoea	0/330 (0%)		0/333 (0%)		2/335 (0.6%)
Lung infiltration	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Pleural effusion	0/330 (0%)		1/333 (0.3%)		0/335 (0%)
Vascular disorders
Hypertension	1/330 (0.3%)		1/333 (0.3%)		1/335 (0.3%)
Hypertensive crisis	0/330 (0%)		0/333 (0%)		2/335 (0.6%)
Peripheral arterial occlusive disease	1/330 (0.3%)		0/333 (0%)		0/335 (0%)
Other (Not Including Serious) Adverse Events
	Indacaterol 150 μg		Salmeterol 50 μg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/330 (20.9%)		68/333 (20.4%)		71/335 (21.2%)
Infections and infestations
Nasopharyngitis	24/330 (7.3%)		29/333 (8.7%)		21/335 (6.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	52/330 (15.8%)		48/333 (14.4%)		58/335 (17.3%)

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 date (i.e., data from all sites) in the clinical trial.