Study of Indacaterol Dosed in the Evening in Patients With Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00615030
• Collaborator: (none)
• Enrollment: 96
• Locations: 7
• Arms: 12
• Duration (Months): 7
• Patients Per Site: 13.7
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This study was conducted to provide detailed information on the efficacy of indacaterol (in terms of the spirometry assessment forced expiratory volume in 1 second [FEV1]) over the full 24-h time period

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Double Blind, Double Dummy, Placebo Controlled, Multicenter, 4 Treatments, 3 Period Incomplete Block Crossover Study to Assess the Efficacy and Safety of Indacaterol 300 µg o.d. Dosed in the Evening in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Salmeterol 50 µg b.i.d. as Active Control
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Indacaterol Morning,Indacaterol Evening, Salmeterol In period I, indacaterol 300 μg once a day in the morning delivered via single dose dry powder inhaler (SDDPI) with a placebo to salmeterol delivered via dry powder inhaler (DPI). Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, Salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and second dose in the evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Evening,Indacaterol Morning, Placebo In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Salmeterol, Placebo, Indacaterol Morning In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose was in the evening along with placebo matching indacaterol delivered by SDDPI. In period II, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Placebo, Salmeterol, Indacaterol Evening In period I, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, salmeterol 50 μg twice daily delivered via dry powder inhaler (DPI). One of the two daily doses of salmeterol was administered in the morning and the second dose was in the evening along with placebo matching indacaterol delivered by SDDPI. In period III, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via dry DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Morning, Placebo, Indacaterol Evening In period I, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, During morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, Patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Evening,Salmeterol, Indacaterol Morning In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period II, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Salmeterol, Indacaterol Evening, Placebo In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Placebo, Indacaterol Morning, Salmeterol In period I, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via dry powder inhaler DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Morning, Salmeterol, Placebo In period I, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Evening, Placebo, Salmeterol In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via dry powder inhaler DPI. In period II, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Salmeterol, Indacaterol Morning, Indacaterol Evening In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Salmeterol; 50 µg twice daily delivered via dry powder inhaler (DPI); Other Names: Serevent® ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI
Experimental: Placebo, Indacaterol Evening, Indacaterol Morning In period, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Drug: Indacaterol; 300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI); Other Names: QAB149 ; Drug: Placebo to Indacaterol; Placebo matching indacaterol was delivered via SDDPI.; Drug: Placebo to Salmeterol; Placebo matching salmeterol was delivered via DPI

Outcome Measures

Primary Outcome Measures

1. Trough Forced Expiratory Volume in 1 Second (FEV1) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo [After 14 days of treatment]

   Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 10 min and 23h 45 min post dose. The primary variable was analyzed using an analysis of covariance (ANCOVA) model with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.

Secondary Outcome Measures

1. Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons [After 14 days of dosing]

   Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. On the morning and evening of Day 15 trough FEV1 (i.e. mean of measurements performed 23 h 10 min and 23 h 45 min post-dose) were assessed. An analysis of covariance (ANCOVA) model was used with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure

• Co-operative outpatients with a diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the Global initiative for chronic obstructive lung disease (GOLD) Guidelines, 2006) and:

• Smoking history of at least 20 pack years

• Post-bronchodilator FEV1 < 80% and ≥30% of the predicted normal value

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

Exclusion criteria:

• Pregnant or lactating females

• Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period

• Patients requiring long term oxygen therapy (>15 h a day)

• Patient who have had a respiratory tract infection 6 weeks prior to V2 (with further criteria)

• Patients with concomitant pulmonary disease, pulmonary tuberculosis, or clinically significant bronchiectasis

• Patients with history of asthma (with further criteria)

• Patients with Type I or uncontrolled type II diabetes.

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

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

• Patient with a history with long QT syndrome or whose QTc interval is prolonged

• Patients with a hypersensitivity to any of the study drugs or drugs with similar chemical structure

• Patients who have had treatment with an investigational drug (with further criteria)

• Patients who have had live attenuated vaccination within 30 days prior to Visit 2, or during run-in period

• Patients with known history of non compliance to medication

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

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Beuvry		France
2	Novartis Investigative Site	Nantes		France
3	Novartis Investigative Site	Berlin		Germany
4	Novartis Investigative Site	Hamburg		Germany
5	Novartis Investigative Site	Leipzig		Germany
6	Novartis Investigative Site	Mainz		Germany
7	Novartis Investigative Site	Barcelona		Spain

Sponsors and Collaborators

• Novartis

Investigators

• Principal Investigator: Novartis Pharmaceuticals, + 41 61 324 1111

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00615030
• Other Study ID Numbers: CQAB149B2305
• First Posted: Feb 14, 2008
• Last Update Posted: Aug 17, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: COPD, bronchodilator, long acting beta agonist, LABA
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Study Results

Participant Flow

Recruitment Details	Patients were randomized to one of the 12 possible treatment sequences of the double-blind 10-week treatment phase (Week 1 - 10). Each treatment sequence was divided into three treatment periods (I/II/III) of 15-day duration each. The first and second treatment period of each sequence was followed by a 2-week washout period.
Pre-assignment Detail	Total 96 patients were randomized; one randomized patient discontinued from the study prior to exposure to study drug because of abnormal test procedure(s) result.

Arm/Group Title	Sequence 1:Indacaterol Morning,Indacaterol Evening, Salmeterol	Sequence 2:Indacaterol Evening,Indacaterol Morning, Placebo	Sequence 3: Salmeterol, Placebo, Indacaterol Morning	Sequence 4: Placebo, Salmeterol, Indacaterol Evening	Sequence 5: Indacaterol Morning, Placebo, Indacaterol Evening	Sequence 6:Indacaterol Evening,Salmeterol, Indacaterol Morning	Sequence 7: Salmeterol, Indacaterol Evening, Placebo	Sequence 8: Placebo, Indacaterol Morning, Salmeterol	Sequence 9:Indacaterol Morning, Salmeterol, Placebo	Sequence 10: Indacaterol Evening, Placebo, Salmeterol	Sequence 11:Salmeterol,Indacaterol Morning,Indacaterol Evening	Sequence 12: Placebo, Indacaterol Evening, Indacaterol Morning
Arm/Group Description	In period I, indacaterol 300 μg once a day in the morning delivered via single dose dry powder inhaler (SDDPI) with a placebo to salmeterol delivered via dry powder inhaler (DPI). Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, Salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and second dose in the evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose was in the evening along with placebo matching indacaterol delivered by SDDPI. In period II, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, salmeterol 50 μg twice daily delivered via dry powder inhaler (DPI). One of the two daily doses of salmeterol was administered in the morning and the second dose was in the evening along with placebo matching indacaterol delivered by SDDPI. In period III, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via dry DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, During morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, Patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period II, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via dry powder inhaler DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period II, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In period, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Period Title: Period I
STARTED	9	8	9	8	9	6	7	7	9	8	8	7
COMPLETED	8	8	9	8	8	5	7	7	8	8	7	6
NOT COMPLETED	1	0	0	0	1	1	0	0	1	0	1	1
Period Title: Period I
STARTED	8	8	9	8	8	5	7	7	8	8	7	6
COMPLETED	8	8	8	7	8	5	6	7	7	8	7	6
NOT COMPLETED	0	0	1	1	0	0	1	0	1	0	0	0
Period Title: Period I
STARTED	8	8	8	7	8	5	6	7	7	8	7	6
COMPLETED	7	8	8	6	8	5	6	7	7	8	7	6
NOT COMPLETED	1	0	0	1	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Total Patients
Arm/Group Description
Overall Participants	95
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (8.70)
Sex: Female, Male (Count of Participants)
Female	15 15.8%
Male	80 84.2%

Outcome Measures

1. Primary Outcome

Title	Trough Forced Expiratory Volume in 1 Second (FEV1) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo
Description	Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 10 min and 23h 45 min post dose. The primary variable was analyzed using an analysis of covariance (ANCOVA) model with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.
Time Frame	After 14 days of treatment

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population included all randomized patients who received at least one dose of study drug. Patients who received only one treatment were also included for calculation of treatment means. This analysis included all patients who received indacaterol in the evening or placebo in their assigned treatment sequence.

Arm/Group Title	Indacaterol Evening	Placebo
Arm/Group Description	Patients were instructed to take morning doses of a placebo to indacaterol delivered via single dose dry powder inhaler (SDDPI) and placebo to salmeterol delivered via dry powder inhaler (DPI). Indacaterol 300 μg once a day in the evening delivered via single dose dry powder inhaler (SDDPI) with placebo to salmeterol delivered via dry powder inhaler (DPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	During evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Measure Participants	63	64
Least Squares Mean (Standard Error) [Liters]	1.57 (0.025)	1.37 (0.025)

2. Secondary Outcome

Title	Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons
Description	Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. On the morning and evening of Day 15 trough FEV1 (i.e. mean of measurements performed 23 h 10 min and 23 h 45 min post-dose) were assessed. An analysis of covariance (ANCOVA) model was used with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.
Time Frame	After 14 days of dosing

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population included all randomized patients who received at least one dose of study drug. Patients who received only one treatment were also included for calculation of treatment means.

Arm/Group Title	Indacaterol Morning	Indacaterol Evening	Salmeterol Morning	Salmeterol Evening	Placebo Morning	Placebo Evening
Arm/Group Description	Indacaterol 300 μg once a day in the morning delivered via single dose dry powder inhaler (SDDPI) with a placebo to salmeterol delivered via dry powder inhaler (DPI). Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via single dose dry powder inhaler (SDDPI) with placebo to salmeterol delivered via dry powder inhaler (DPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In the morning, Salmeterol 50 μg delivered via dry powder inhaler (DPI) along with placebo matching indacaterol via SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	In the evening, Salmeterol 50 μg delivered via dry powder inhaler (DPI) along with placebo matching indacaterol via SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via manufacturer's proprietary DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.	Placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via manufacturer's proprietary DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Measure Participants	65	63	65	65	66	64
Least Squares Mean (Standard Error) [Liters]	1.56 (0.025)	1.57 (0.025)	1.51 (0.025)	1.46 (0.025)	1.36 (0.025)	1.37 (0.025)

Adverse Events

Time Frame	10 weeks
Adverse Event Reporting Description	In the safety population, all patients were analyzed according to treatment received.
Arm/Group Title	Indacaterol Evening		Indacaterol Morning		Salmeterol		Placebo
Arm/Group Description	Patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via single dose dry powder inhaler (SDDPI) with placebo to salmeterol delivered via dry powder inhaler (DPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. All patients were provided with a SABA for use (if needed) as rescue medication throughout the study.		Indacaterol 300 μg once a day in the morning delivered via single dose dry powder inhaler (SDDPI) with a placebo to salmeterol delivered via dry powder inhaler (DPI). Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. All patients were provided with a SABA for use (if needed) as rescue medication throughout the study.		Salmeterol 50 μg twice daily delivered via dry powder inhaler (DPI). One of the two daily doses of salmeterol was administered in the morning along with placebo matching indacaterol delivered by single dose dry powder inhaler (SDDPI). The second dose of salmeterol was administered in the evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. All patients were provided with a SABA for use (if needed) as rescue medication throughout the study.		During morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. All patients were provided with a SABA for use (if needed) as rescue medication throughout the study.
All Cause Mortality
	Indacaterol Evening		Indacaterol Morning		Salmeterol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol Evening		Indacaterol Morning		Salmeterol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		1/68 (1.5%)		0/68 (0%)		0/68 (0%)
Injury, poisoning and procedural complications
Rib fracture	0/65 (0%)		1/68 (1.5%)		0/68 (0%)		0/68 (0%)
Other (Not Including Serious) Adverse Events
	Indacaterol Evening		Indacaterol Morning		Salmeterol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/65 (15.4%)		4/68 (5.9%)		3/68 (4.4%)		5/68 (7.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	5/65 (7.7%)		0/68 (0%)		2/68 (2.9%)		5/68 (7.4%)
Cough	5/65 (7.7%)		4/68 (5.9%)		1/68 (1.5%)		0/68 (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 (i.e., data from all sites) in the clinical trial.