Dose Ranging Study for Indacaterol in Japanese Asthma Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00403754
• Collaborator: (none)
• Enrollment: 41
• Locations: 8
• Arms: 4
• Duration (Months): 12
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study was designed to provide data about the safety and efficacy of 3 doses of indacaterol (150, 300, and 600 µg) in Japanese asthma patients so that an optimal dose, or doses, could be chosen for testing in later studies.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Indacaterol; Drug: Placebo; Drug: Salmeterol	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, 4-period 4-treatment Crossover, Multicenter, Single-dose, Dose-ranging Study Followed by a Single Day's Treatment With Open Label Salmeterol Bid (100 µg/Day), to Assess the Efficacy and Safety of 3 Doses of Indacaterol (150, 300, & 600 µg) Delivered Via Single Dose Dry Powder Inhaler (SDDPI) in Japanese Asthma Patients
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo-Ind 150 μg-Ind 300 μg-Ind 600 μg-Salmeterol In treatment period 1: patients received 2 placebo capsules; in treatment period 2: patients received 1 indacaterol (Ind) 150 μg capsule + 1 placebo capsule; in treatment period 3: patients received 1 indacaterol 300 μg capsule + 1 placebo capsule; and in treatment period 4: patients received 2 indacaterol 300 μg capsules. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Drug: Indacaterol; In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).; Other Names: QAB149 ; Drug: Placebo; Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).; Drug: Salmeterol; Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.; Other Names: Serevent
Experimental: Ind 150 μg-Ind 600 μg-Placebo-Ind 300 μg-Salmeterol In treatment period 1: patients received 1 indacaterol (Ind) 150 μg capsule + 1 placebo capsule; in treatment period 2: patients received 2 indacaterol 300 μg capsules; in treatment period 3: patients received 2 placebo capsules; and in treatment period 4: patients received 1 indacaterol 300 μg capsule + 1 placebo capsule. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Drug: Indacaterol; In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).; Other Names: QAB149 ; Drug: Placebo; Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).; Drug: Salmeterol; Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.; Other Names: Serevent
Experimental: Ind 300 μg-Placebo-Ind 600 μg-Ind 150 μg-Salmeterol In treatment period 1: patients received 1 indacaterol (Ind) 300 μg capsule + 1 placebo capsule; in treatment period 2: patients received 2 placebo capsules; in treatment period 3: patients received 2 indacaterol 300 μg capsules; and in treatment period 4: patients received 1 indacaterol 150 μg capsule + 1 placebo capsule. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation, device on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Drug: Indacaterol; In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).; Other Names: QAB149 ; Drug: Placebo; Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).; Drug: Salmeterol; Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.; Other Names: Serevent
Experimental: Ind 600 μg-Ind 300 μg-Ind 150 μg-Placebo-Salmeterol In treatment period 1: patients received 2 indacaterol (Ind) 300 μg capsules; in treatment period 2: patients received 1 indacaterol 300 μg capsule + 1 placebo capsule; in treatment period 3: patients received 1 indacaterol 150 μg capsule + 1 placebo capsule; and in treatment period 4: patients received 2 placebo capsules. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Drug: Indacaterol; In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).; Other Names: QAB149 ; Drug: Placebo; Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).; Drug: Salmeterol; Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.; Other Names: Serevent

Outcome Measures

Primary Outcome Measures

1. Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2 [22, 23, and 24 hours post-dose on Day 2]

   Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC22-24h) of FEV1 values taken at 22, 23 and 24 hours post dose, was calculated based on the trapezoidal rule. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.

Secondary Outcome Measures

1. Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 [5, 15, and 30 minutes; and 1, 2, 4, 8, and 12 hours post-dose on Day 1; and 22, 23, and 24 hours post-dose on Day 2]

   Spirometry was conducted according to internationally accepted standards. FEV1 by time point was calculated using a mixed model with (period) baseline, defined as the value measured prior to the first study drug intake in the period, as a covariate.

2. Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 [5 minutes to 4 hours post-dose on Day 1]

   Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.

3. Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes Post-dose on Day 1 to 24 Hours Post-dose on Day 2 [5 minutes to 12 hours post-dose on Day 1; and 22 to 24 hours post-dose on Day 2]

   Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC0-24h) of FEV1 values taken at pre-dose to 24 hours post dose was calculated based on the trapezoidal rule. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female Japanese asthmatic patients aged 18 to 75 years old.

Exclusion Criteria:

• Patients who have been hospitalized or had emergency room treatment for an acute asthma attack in the 6 months prior to the first day of screening or during the screening period.

• Patients who have used tobacco products within 6 months prior to the first day of screening or have a smoking history of greater than 10 pack years.

• Patients with a history of malignancy with the exception of localized basal cell carcinoma of the skin.

• Pregnant or nursing (lactating) women.

• Patients who have had treatment with disallowed medications including investigational drug.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Kasukabe		Japan
2	Novartis Investigator Site	Kishiwada		Japan
3	Novartis Investigative Site	Shimotsuga		Japan
4	Novartis Investigator Site	Suita		Japan
5	Novartis Investigative Site	Tokyo		Japan
6	Novartis	Tokyo		Japan
7	Novartis Investigator Site	Wakayama		Japan
8	Novartis Investigator Site	Yokohama		Japan

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Novartis Pharmaceuticals Japan, Novartis Pharmaceuticals Japan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00403754
• Other Study ID Numbers: CQAB149A1202
• First Posted: Nov 27, 2006
• Last Update Posted: Aug 17, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: asthma; QAB149; indacaterol; long acting β2-agonist; bronchodilator
• Additional relevant MeSH terms: Asthma; Salmeterol Xinafoate

Study Results

Participant Flow

Pre-assignment Detail	A 14 day eligibility screening period insured all participants were stable on their permissible asthma treatment before proceeding onto core study drug treatment.

Arm/Group Title	Placebo-Ind 150 μg-Ind 300 μg-Ind 600 μg-Salmeterol	Ind 150 μg-Ind 600 μg-Placebo-Ind 300 μg-Salmeterol	Ind 300 μg-Placebo-Ind 600 μg-Ind 150 μg-Salmeterol	Ind 600 μg-Ind 300 μg-Ind150 μg-Placebo-Salmeterol
Arm/Group Description	In treatment period 1: patients received 2 placebo capsules; in treatment period 2: patients received 1 indacaterol (Ind) 150 μg capsule + 1 placebo capsule; in treatment period 3: patients received 1 indacaterol 300 μg capsule + 1 placebo capsule; and in treatment period 4: patients received 2 indacaterol 300 μg capsules. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	In treatment period 1: patients received 1 indacaterol (Ind) 150 μg capsule + 1 placebo capsule; in treatment period 2: patients received 2 indacaterol 300 μg capsules; in treatment period 3: patients received 2 placebo capsules; and in treatment period 4: patients received 1 indacaterol 300 μg capsule + 1 placebo capsule. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	In treatment period 1: patients received 1 indacaterol (Ind) 300 μg capsule + 1 placebo capsule; in treatment period 2: patients received 2 placebo capsules; in treatment period 3: patients received 2 indacaterol 300 μg capsules; and in treatment period 4: patients received 1 indacaterol 150 μg capsule + 1 placebo capsule. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation, device on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use t	In treatment period 1: patients received 2 indacaterol (Ind) 300 μg capsules; in treatment period 2: patients received 1 indacaterol 300 μg capsule + 1 placebo capsule; in treatment period 3: patients received 1 indacaterol 150 μg capsule + 1 placebo capsule; and in treatment period 4: patients received 2 placebo capsules. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use t
Period Title: Core Treatment Period 1
STARTED	11	10	9	11
COMPLETED	11	9	9	11
NOT COMPLETED	0	1	0	0
Period Title: Core Treatment Period 1
STARTED	11	9	9	11
COMPLETED	11	9	8	11
NOT COMPLETED	0	0	1	0
Period Title: Core Treatment Period 1
STARTED	11	9	8	11
COMPLETED	11	9	8	11
NOT COMPLETED	0	0	0	0
Period Title: Core Treatment Period 1
STARTED	11	9	8	11
COMPLETED	11	9	8	11
NOT COMPLETED	0	0	0	0
Period Title: Core Treatment Period 1
STARTED	11	9	8	11
COMPLETED	11	9	8	11
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	The entire study population included all 4 treatment groups who received indacaterol 150 µg, 300 µg, and 600 µg and placebo via a single dose dry powder inhaler (SDDPI) in the 4 different sequences of the core phase. Two capsules of study medication were inhaled in the morning on Day 1 of each treatment period. Following the core phase patients continued to the Salmeterol open label phase. Salmeterol was inhaled via a Diskus inhalation device 50 µg in the morning and 50 µg 12 hours post initial dose on Day 1. Patients received each treatment only once. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.8 (14.90)
Sex: Female, Male (Count of Participants)
Female	21 51.2%
Male	20 48.8%

Outcome Measures

1. Primary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2
Description	Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC22-24h) of FEV1 values taken at 22, 23 and 24 hours post dose, was calculated based on the trapezoidal rule. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.
Time Frame	22, 23, and 24 hours post-dose on Day 2

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Indacaterol 600 µg	Indacaterol 300 µg	Indacaterol 150 µg	Placebo	Salmeterol 100 μg
Arm/Group Description	Two capsules of indacaterol 300 µg were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 600 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 300 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 300 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 150 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 150 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Two placebo capsules were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Placebo was administered to each patient only once. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Open label Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.
Measure Participants	39	40	40	40	39
Least Squares Mean (Standard Error) [Liters]	2.31 (0.023)	2.28 (0.022)	2.24 (0.022)	2.06 (0.022)	2.23 (0.022)

2. Secondary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2
Description	Spirometry was conducted according to internationally accepted standards. FEV1 by time point was calculated using a mixed model with (period) baseline, defined as the value measured prior to the first study drug intake in the period, as a covariate.
Time Frame	5, 15, and 30 minutes; and 1, 2, 4, 8, and 12 hours post-dose on Day 1; and 22, 23, and 24 hours post-dose on Day 2

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Indacaterol 600 µg	Indacaterol 300 µg	Indacaterol 150 µg	Placebo	Salmeterol 100 μg
Arm/Group Description	Two capsules of indacaterol 300 µg were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 600 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 300 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 300 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 150 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 150 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Two placebo capsules were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Placebo was administered to each patient only once. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Open label Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.
Measure Participants	39	40	40	40	39
5 minutes	2.25	2.20	2.19	2.04	2.13
15 minutes	2.33	2.28	2.27	2.05	2.19
30 minutes	2.37	2.33	2.30	2.07	2.24
1 hour	2.41	2.35	2.32	2.09	2.29
2 hours	2.45	2.39	2.38	2.13	2.34
4 hours	2.42	2.39	2.35	2.10	2.34
8 hours	2.37	2.35	2.28	2.06	2.25
12 hours	2.33	2.30	2.24	2.00	2.20
22 hours	2.30	2.25	2.20	2.01	2.18
23 hours	2.32	2.28	2.25	2.06	2.23
24 hours	2.32	2.29	2.26	2.09	2.27

3. Secondary Outcome

Title	Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1
Description	Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.
Time Frame	5 minutes to 4 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Indacaterol 600 µg	Indacaterol 300 µg	Indacaterol 150 µg	Placebo	Salmeterol 100 μg
Arm/Group Description	Two capsules of indacaterol 300 µg were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 600 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 300 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 300 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 150 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 150 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Two placebo capsules were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Placebo was administered to each patient only once. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Open label Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.
Measure Participants	39	40	40	40	39
Least Squares Mean (Standard Error) [Liters]	2.49 (0.018)	2.44 (0.018)	2.41 (0.018)	2.19 (0.18)	2.39 (0.018)

4. Secondary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes Post-dose on Day 1 to 24 Hours Post-dose on Day 2
Description	Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC0-24h) of FEV1 values taken at pre-dose to 24 hours post dose was calculated based on the trapezoidal rule. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.
Time Frame	5 minutes to 12 hours post-dose on Day 1; and 22 to 24 hours post-dose on Day 2

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Indacaterol 600 µg	Indacaterol 300 µg	Indacaterol 150 µg	Placebo	Salmeterol 100 μg
Arm/Group Description	Two capsules of indacaterol 300 µg were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 600 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 300 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 300 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	One capsule of indacaterol 150 µg and 1 placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Indacaterol 150 µg was administered only once to each patient. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Two placebo capsules were inhaled using a single dose dry powder inhaler (SDDPI) device in the morning on Day 1 of the treatment period. Placebo was administered to each patient only once. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.	Open label Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.
Measure Participants	39	40	40	40	39
Least Squares Mean (Standard Error) [Liters]	2.35 (0.022)	2.31 (0.021)	2.26 (0.021)	2.04 (0.021)	2.24 (0.021)

Adverse Events

Adverse Event Reporting Description	Safety Population included all participants who received at least one dose of study drug.
Arm/Group Title	Indacaterol 150 μg		Indacaterol 300 μg		Indacaterol 600 μg		Placebo		Salmeterol 100 μg
Arm/Group Description	1 Indacaterol 150 μg capsule + 1 Placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of the Indacaterol 150 μg treatment period. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.		1 Indacaterol 300 μg capsules + 1 Placebo capsule were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of the Indacaterol 300 μg treatment period. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.		2 Indacaterol 300 μg capsules were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of the Indacaterol 600 μg treatment period. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.		2 Placebo capsules were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of the Placebo treatment period. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.		Open label Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study.
All Cause Mortality
	Indacaterol 150 μg		Indacaterol 300 μg		Indacaterol 600 μg		Placebo		Salmeterol 100 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol 150 μg		Indacaterol 300 μg		Indacaterol 600 μg		Placebo		Salmeterol 100 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)		0/39 (0%)		0/40 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Indacaterol 150 μg		Indacaterol 300 μg		Indacaterol 600 μg		Placebo		Salmeterol 100 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/40 (35%)		14/40 (35%)		14/39 (35.9%)		6/40 (15%)		1/39 (2.6%)
Nervous system disorders
HEADACHE	2/40 (5%)		2/40 (5%)		1/39 (2.6%)		3/40 (7.5%)		1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
COUGH	14/40 (35%)		13/40 (32.5%)		14/39 (35.9%)		3/40 (7.5%)		0/39 (0%)
OBSTRUCTIVE AIRWAYS DISORDER	1/40 (2.5%)		1/40 (2.5%)		2/39 (5.1%)		0/40 (0%)		0/39 (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.