Safety of Exercise and High-dose Salbutamol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Receiving Therapeutic Doses of Indacaterol (QAB 149) and Salmeterol

Part 1: Sequence 'A' consisted of - Period 1, patient received a single inhaled dose of indacaterol 300μg capsule via the Concept1 inhaler device. Period 2, patient received single dose of salmeterol 50μg via Diskus dry powder inhaler (DPI). Period 3, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device.

Part 2: Sequence 'A' consisted of - Period 1, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 3, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

Part 1: Sequence 'B' consisted of - Period 1, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device. Period 2, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patient received single dose of salmeterol 50μg via Diskus DPI.

Part 2: Sequence 'B' consisted of - Period 1, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 3, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

Part 1: Sequence 'C' consisted of - Period 1, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patient received single dose of salmeterol 50μg via Diskus DPI. Period 3, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device.

Part 2: Sequence 'C' consisted of - Period 1, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 2, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 3, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device . In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

Part 1: Sequence 'D' consisted of - Period 1, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 2, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device. Period 3, patient received single dose of salmeterol 50μg via Diskus DPI.

Part 2: Sequence 'D' consisted of - Period 1, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 2, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

Part 1: Sequence 'E' consisted of - Period 1, patient received single dose of salmeterol 50μg via Diskus DPI. Period 2, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device. Period 3, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device.

Part 2: Sequence 'E' consisted of - Period 1, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 2, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

Part 1: Sequence 'F' consisted of - Period 1, patient received single dose of salmeterol 50μg via Diskus DPI. Period 2, patient received single dose of indacaterol matching placebo via the Concept1 inhaler device. Period 3, patient received a single inhaled dose of indacaterol 300μg capsule administered via the Concept1 inhaler device.

Part 2: Sequence 'F' consisted of - Period 1, patients received morning and evening single inhalational dose of salmeterol 50μg via Diskus DPI. Period 2, patients received single inhalation dose of indacaterol matching placebo in morning and evening via Concept1 device. Period 3, patients received a morning single inhalational dose of indacaterol 300μg and an evening single inhalation dose of indacaterol matching placebo via the Concept1 inhaler device. In Part 2 of the study, at 20 minutes following each dose, patients received three doses of nebulized salbutamol 2.5 mg at 20 minute intervals.

The percentage of patients with an increase of >= 10 beats per minute (bpm) in their heart rate (HR) following treatment with indacaterol and salmeterol compared to treatment with placebo over 24 hours in Part 2 was determined.

• 0-12 hours: post first dose measurements up to second dose
• 12-24 hours: post second dose measurement up to and including the 24 hour measurement
• 0-24 hours: all post dose measurements up to and including the 24 hour measurement

Change in heart rate is calculated from the 1.5 hour post dose to the maximum heart rate during exercise.

Analysis of covariance included treatment and period as fixed effects, subject as random effect and 1.5 hour pre-exercise/post dose heart rate as a covariate.