INSIST: Safety and Efficacy of Indacaterol Once Daily Versus Salmeterol Twice Daily in Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00821093
• Collaborator: (none)
• Enrollment: 1,123
• Locations: 144
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study compared the safety and efficacy of indacaterol 150 µg taken once daily (o.d.) versus salmeterol 50 µg taken twice daily (b.i.d) in patients 40 years old or older 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: 1123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12 Week Treatment, Multi-center, Randomized, Parallel Group, Double Blind, Double Dummy Study to Assess the Superiority of Indacaterol (150 µg o.d.) Via a SDDPI in Patients With Moderate to Severe COPD, Using Salmeterol (50 µg b.i.d.) as an Active Comparator Delivered Via a DISKUS Inhaler
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Indacaterol 150 µg Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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 150 µg; Indacaterol 150 μg was provided in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to salmeterol; Placebo to salmeterol was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]).
Active Comparator: Salmeterol 50 µg Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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: Salmeterol 50 µg; Salmeterol 50 μg was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]).; Drug: Placebo to indacaterol; Placebo to indacaterol was provided in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).

Outcome Measures

Primary Outcome Measures

1. Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84) [From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84)]

   FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; 1, 2, 3, 4, and 8 hours; 11 hours 10 minutes and 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.

Secondary Outcome Measures

1. Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85) [24 hours post-dose at the end of the study (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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol 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:

• Adults aged ≥ 40 years

• Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the GOLD Guidelines, 2007) and:

• Smoking history of at least 10 pack years

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

• Post-bronchodilator FEV1/FVC (forced vital capacity) < 70% at screening

Exclusion Criteria:

• Patients who have received systemic corticosteroids for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period

• Patients requiring long-term oxygen therapy (> 15 h a day) for chronic hypoxemia

• Patients who have 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

• Any patient with active cancer or a history of cancer with less than 5 years disease-free survival time

• Patients with a history of long QT syndrome or whose QTc interval (Fridericia's) measured at screening is prolonged

• Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period

• Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	Anniston	Alabama	United States	36207-5710
2	Novartis Investigator Site	Fairhope	Alabama	United States	36532
3	Novartis Investigator Site	Jasper	Alabama	United States	35501
4	Novartis Investigator Site	Mobile	Alabama	United States	36604
5	Novartis Investigator Site	Glendale	Arizona	United States	85306
6	Novartis Investigator Site	Phoenix	Arizona	United States	85006
7	Novartis Investigator Site	Buena Park	California	United States	90620
8	Novartis Investigator Site	Encinitas	California	United States	92024
9	Novartis Investigator Site	Fullerton	California	United States	92535
10	Novartis Investigator Site	Rancho Mirage	California	United States	92270
11	Novartis Investigator Site	Riverside	California	United States	92506
12	Novartis Investigator Site	San Diego	California	United States	92120
13	Novartis Investigator Site	Torrance	California	United States	90505
14	Novartis Investigator Site	Walnut Creek	California	United States	94598
15	Novartis Investigator Site	Fort Collins	Colorado	United States	80528
16	Novartis Investigative Site	Wheat Ridge	Colorado	United States	80033
17	Novartis Investigative Site	Stamford	Connecticut	United States	06902
18	Novartis Investigative Site	Newark	Delaware	United States	19713
19	Novartis Investigative Center	Clearwater	Florida	United States	33765
20	Novartis Investigative Site	Pensacola	Florida	United States	32504
21	Novartis Investigative Site	Pensacola	Florida	United States	32514
22	Novartis Investigative Site	South Miami	Florida	United States	33143
23	Novartis Investigative Site	Tamarac	Florida	United States	33321
24	Novartis Investigative Site	Tampa	Florida	United States	33603
25	Novartis Investigative Site	Tampa	Florida	United States	33613
26	Novartis Investigative Site	Marietta	Georgia	United States	30060
27	Novartis Investigator Site	Normal	Illinois	United States	61761
28	Novartis Investigator Site	River Forest	Illinois	United States	60305
29	Novartis Investigator Site	Skokie	Illinois	United States	60076
30	Novartis Investigator Site	Olathe	Kansas	United States	66061
31	Novartis Investigator Site	Wichita	Kansas	United States	67207
32	Novartis Investigator Site	Madisonville	Kentucky	United States	42431
33	Novartis Investigator Site	New Orleans	Louisiana	United States	70115
34	Novartis Investigator Site	Opelousas	Louisiana	United States	70570
35	Novartis Investigative Site	Baltimore	Maryland	United States	21236
36	Novartis Investigator Site	Ann Arbor	Michigan	United States	48106
37	Novartis Investigator Site	Livonia	Michigan	United States	48152
38	Novartis Investigator Site	Minneapolis	Minnesota	United States	55407
39	Novartis Investigator Site	St Charles	Missouri	United States	63301-2847
40	Novartis Investigator Site	St Louis	Missouri	United States	63141
41	Novartis Investigator Site	Lincoln	Nebraska	United States	68510
42	Novartis Investigator Site	Omaha	Nebraska	United States	68134
43	Novartis Investigator Site	Henderson	Nevada	United States	89014
44	Novartis Investigative Site	Reno	Nevada	United States	89502
45	Novartis Investigative Site	Cherry Hill	New Jersey	United States	08003
46	Novartis Investigative Site	Summit	New Jersey	United States	07901
47	Novartis Investigator Site	Albuquerque	New Mexico	United States	87108
48	Novartis Investigative Site	Larchmont	New York	United States	10538
49	Novartis Investigative Site	Charlotte	North Carolina	United States	28207
50	Novartis Investigative Site	Hickory	North Carolina	United States	28601
51	Novartis Investigative Site	Raleigh	North Carolina	United States	27607
52	Novartis Investigative Site	Shelby	North Carolina	United States	28150
53	Novartis Investigator Site	Cincinnati	Ohio	United States	45245
54	Novartis Investigator Site	Columbus	Ohio	United States	42313
55	Novartis Investigator Site	Willoughby Hills	Ohio	United States	44094
56	Novartis Investigator Site	Tulsa	Oklahoma	United States	74135-2920
57	Novartis Investigator Site	Eugene	Oregon	United States	97404
58	Novartis Investigator Site	Medford	Oregon	United States	97504-8741
59	Novartis Investigator Site	Portland	Oregon	United States	97213
60	Novartis Investigative Site	Erie	Pennsylvania	United States	16506
61	Novartis Investigative Site	Charleston	South Carolina	United States	29412
62	Novartis Investigative Site	Greenville	South Carolina	United States	29615
63	Novartis Investigative Site	North Charleston	South Carolina	United States	29406-7108
64	Novartis Investigative site	Spartanburg	South Carolina	United States	29303
65	Novartis Investigative Site	Union	South Carolina	United States	29379
66	Novartis Investigator Site	El Paso	Texas	United States	79903
67	Novartis Investigator Site	Fort Worth	Texas	United States	76104
68	Novartis Investigator Site	Houston	Texas	United States	77024
69	Novartis Investigator Site	San Antonio	Texas	United States	78212
70	Novartis Investigative Site	Abingdon	Virginia	United States	24210
71	Novartis Investigative Site	Richmond	Virginia	United States	23229
72	Novartis Investigator Site	Spokane	Washington	United States	99204
73	Novartis Investigator Site	Tacoma	Washington	United States	98405-4266
74	Novartis Investigator Site	Milwaukee	Wisconsin	United States	53209-0996
75	Novartis Investigator Site	Cvikov		Czech Republic
76	Novartis Investigator Site	Kyjov		Czech Republic
77	Novartis Investigator Site	Lovosice		Czech Republic
78	Novartis Investigator Site	Neratovice		Czech Republic
79	Novartis Investigator Site	Ostrava		Czech Republic
80	Novartis Investigator Site	Pardubice		Czech Republic
81	Novartis Investigator Site	Prague		Czech Republic
82	Novartis Investigator Site	Teplice		Czech Republic
83	Novartis Investigative Site	Aschaffenburg		Germany
84	Novartis Investigative Site	Augsburg		Germany
85	Novartis Investigative Site	Backnang		Germany
86	Novartis Investigative Site	Berlin		Germany
87	Novartis Investigator Site	Berlin		Germany
88	Novartis Investigative Site	Bielefeld		Germany
89	Novartis Investigative Site	Borstel		Germany
90	Novartis Investigative Site	Dortmund		Germany
91	Novartis Investigative Site	Duisburg		Germany
92	Novartis Investigator Site	Frankfurt		Germany
93	Novartis Investigative Site	Geesthacht		Germany
94	Novartis Investigative Site	Hagen		Germany
95	Novartis Investigative Site	Hamburg		Germany
96	Novartis Investigative Site	Karlsruhe		Germany
97	Novartis Investigative Site	Kiel		Germany
98	Novartis Investigator Site	Leipzig		Germany
99	Novartis Investigative Site	Lübeck		Germany
100	Novartis Investigative Site	Mainz		Germany
101	Novartis Investigative Site	Marburg		Germany
102	Novartis Investigative Site	Neumuenster		Germany
103	Novartis Investigative SIte	Oschersleben		Germany
104	Novartis Investigative Site	Ruedersdorf		Germany
105	Novartis Investigative Site	Weyhe		Germany
106	Novartis Investigative Site	Wiesloch		Germany
107	Novartis Investgative Site	Witten		Germany
108	Novartis Investigator Site	Budapest		Hungary
109	Novartis Investigator Site	Debrecen		Hungary
110	Novartis Investigative Site	Deszk		Hungary
111	Novartis Investigator Site	Mosonmagyarovar		Hungary
112	Novartis Investigator Site	Nyiregyhaza		Hungary
113	Novartis Investigator Site	Tatabanya		Hungary
114	Novartis Investigator Site	Torokbalint		Hungary
115	Novartis Investigator Site	Chennai		India
116	Novartis Investigator Site	Hyderabad		India
117	Novartis Investigator Site	Jaipur		India
118	Novartis Investigator Site	Mangalore		India
119	Novartis Investigator Site	Panjim		India
120	Novartis Investigator Site	Pune		India
121	Novartis Investigator Site	Trivandrum		India
122	Novartis Investigator Site	Vellore		India
123	Novartis Investigative Site	Bojnice		Slovakia
124	Novartis Investigator Site	Bratislava		Slovakia
125	Novartis Investigative Site	Humenne		Slovakia
126	Novartis Investigative Site	Kosice		Slovakia
127	Novartis Investigator Site	Liptovsky Hradok		Slovakia
128	Novartis Investigative Site	Partizanske		Slovakia
129	Novartis Investigative Site	Spisska Nova Ves		Slovakia
130	Novartis Investigator Site	Alicante		Spain
131	Novartis Investigative Site	Barcelona		Spain
132	Novartis Investigative Site	Caceres		Spain
133	Novartis Investigative Site	Cordoba		Spain
134	Novartis Investigative Site	La Coruna		Spain
135	Novartis Investigative Site	Merida		Spain
136	Novartis Investigative Site	Orense		Spain
137	Novartis Investigative Site	Valencia		Spain
138	Novartis Investigative Site	Altunizade		Turkey
139	Novartis Investigator Site	Istanbul		Turkey
140	Novartis Investigator Site	Izmir		Turkey
141	Novartis Investigator Site	Kartal/Istanbul		Turkey
142	Novartis Investigative Site	Kinikli / Denizli		Turkey
143	Novartis Investigative Site	Mersin		Turkey
144	Novartis Investigator Site	Yenisehir/Izmir		Turkey

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00821093
• Other Study ID Numbers: CQAB149B2349; 2008-005146-23
• First Posted: Jan 13, 2009
• Last Update Posted: Aug 18, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: respiratory; dyspnea; breathlessness; COPD; indacaterol; long-acting β2-agonist
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Study Results

Participant Flow

Pre-assignment Detail	Out of total 1123 randomized patients, two patients withdrew from study prior to exposure to study drug.

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg
Arm/Group Description	Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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 salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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	560	563
Exposed to Drug	559	562
COMPLETED	511	523
NOT COMPLETED	49	40

Baseline Characteristics

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg	Total
Arm/Group Description	Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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 salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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	559	562	1121
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.4 (8.86)	63.2 (8.69)	62.8 (8.78)
Sex: Female, Male (Count of Participants)
Female	189 33.8%	147 26.2%	336 30%
Male	370 66.2%	415 73.8%	785 70%

Outcome Measures

1. Primary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84)
Description	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; 1, 2, 3, 4, and 8 hours; 11 hours 10 minutes and 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.
Time Frame	From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84)

Outcome Measure Data

Analysis Population Description

Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg
Arm/Group Description	Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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 salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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	504	488
Least Squares Mean (Standard Error) [Liters]	1.47 (0.009)	1.41 (0.010)

2. Secondary Outcome

Title	Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.
Time Frame	24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85)

Outcome Measure Data

Analysis Population Description

Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Arm/Group Title	Indacaterol 150 μg	Salmeterol 50 μg
Arm/Group Description	Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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 salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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	522	512
Least Squares Mean (Standard Error) [Liters]	1.41 (0.009)	1.35 (0.010)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	The Safety set included all patients who received at least one dose of study drug.
Arm/Group Title	Indacaterol 150 μg		Salmeterol 50 μg
Arm/Group Description	Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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 salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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 150 μg		Salmeterol 50 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol 150 μg		Salmeterol 50 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/559 (3.6%)		16/562 (2.8%)
Cardiac disorders
Acute coronary syndrome	0/559 (0%)		1/562 (0.2%)
Acute myocardial infarction	1/559 (0.2%)		0/562 (0%)
Angina pectoris	2/559 (0.4%)		0/562 (0%)
Atrial fibrillation	1/559 (0.2%)		0/562 (0%)
Atrial flutter	1/559 (0.2%)		0/562 (0%)
Cardiac failure congestive	1/559 (0.2%)		0/562 (0%)
Cardiopulmonary failure	1/559 (0.2%)		0/562 (0%)
Coronary artery disease	0/559 (0%)		1/562 (0.2%)
Myocardial infarction	1/559 (0.2%)		0/562 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/559 (0%)		1/562 (0.2%)
General disorders
Asthenia	0/559 (0%)		1/562 (0.2%)
Pyrexia	1/559 (0.2%)		0/562 (0%)
Immune system disorders
Contrast media allergy	0/559 (0%)		1/562 (0.2%)
Infections and infestations
Bronchitis	0/559 (0%)		1/562 (0.2%)
Cellulitis	1/559 (0.2%)		0/562 (0%)
Pneumonia	1/559 (0.2%)		0/562 (0%)
Upper respiratory tract infection bacterial	2/559 (0.4%)		0/562 (0%)
Injury, poisoning and procedural complications
Fall	1/559 (0.2%)		0/562 (0%)
Lower limb fracture	1/559 (0.2%)		0/562 (0%)
Skin laceration	1/559 (0.2%)		0/562 (0%)
Investigations
Weight decreased	1/559 (0.2%)		1/562 (0.2%)
Metabolism and nutrition disorders
Hyponatraemia	0/559 (0%)		1/562 (0.2%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/559 (0%)		1/562 (0.2%)
Pathological fracture	1/559 (0.2%)		0/562 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/559 (0.2%)		0/562 (0%)
Lung adenocarcinoma	1/559 (0.2%)		0/562 (0%)
Lung neoplasm	0/559 (0%)		1/562 (0.2%)
Metastases to spine	1/559 (0.2%)		0/562 (0%)
Non-Hodgkin's lymphoma	1/559 (0.2%)		0/562 (0%)
Nervous system disorders
Cerebral infarction	1/559 (0.2%)		0/562 (0%)
Cerebrovascular accident	1/559 (0.2%)		0/562 (0%)
Hemiparesis	1/559 (0.2%)		1/562 (0.2%)
Ischaemic stroke	0/559 (0%)		1/562 (0.2%)
Paraesthesia	1/559 (0.2%)		0/562 (0%)
Radicular syndrome	0/559 (0%)		1/562 (0.2%)
Spinal cord compression	1/559 (0.2%)		0/562 (0%)
Syncope	0/559 (0%)		1/562 (0.2%)
Transient ischaemic attack	1/559 (0.2%)		0/562 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	4/559 (0.7%)		7/562 (1.2%)
Respiratory failure	0/559 (0%)		2/562 (0.4%)
Vascular disorders
Peripheral arterial occlusive disease	1/559 (0.2%)		0/562 (0%)
Other (Not Including Serious) Adverse Events
	Indacaterol 150 μg		Salmeterol 50 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/559 (0%)		0/562 (0%)

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