A Crossover Study to Determine the 24 Hour Lung Function Profile of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
=================
Brief Summary
-----------------
This study was conducted to provide detailed information on the efficacy of indacaterol in terms of its effect on spirometry assessed forced expiratory volume in 1 second (FEV1) over a 24 hour time period.

Official Title
-----------------
A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, 3-period, 14-day Crossover Study to Determine the 24 Hour Lung Function Profile of Indacaterol (300 µg Once Daily [od]) in Patients With Moderate-to-severe COPD, Using Open-label Salmeterol (50 µg Twice Daily [Bis in Die, Bid]) as Active Control

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Indacaterol 300 μg
* Drug: Placebo to indacaterol
* Drug: Salmeterol 50 μg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% of the predicted normal value Post-bronchodilator FEV1/FVC (forced vital capacity) < 70% Exclusion Criteria: Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period Patients requiring long-term oxygen therapy (> 15 hours 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 (Bazett's) measured at screening or randomization 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.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol 300 μg - placebo to indacaterol - salmeterol 50 μg<br>In treatment period 1, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received placebo to indacaterol once daily for 14 days via SDDPI; and in treatment period 3, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI). There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Salmeterol 50 μg<br>* Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).<br>|
| Experimental: Placebo to indacaterol - salmeterol 50 μg - indacaterol 300 μg<br>In treatment period 1, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); and in treatment period 3, patients received indacaterol 300 μg once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Salmeterol 50 μg<br>* Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).<br>|
| Experimental: Salmeterol 50 μg - indacaterol 300 μg - placebo to indacaterol<br>In treatment period 1, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); in treatment period 2, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); and in treatment period 3, patients received placebo to indacaterol once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Salmeterol 50 μg<br>* Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).<br>|
| Experimental: Placebo to indacaterol - indacaterol 300 μg - salmeterol 50 μg<br>In treatment period 1, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received indacaterol 300 μg once daily for 14 days via SDDPI; and in treatment period 3, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI). There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Salmeterol 50 μg<br>* Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).<br>|
| Experimental: Indacaterol 300 μg - salmeterol 50 μg - placebo to indacaterol<br>In treatment period 1, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); and in treatment period 3, patients received placebo to indacaterol once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Salmeterol 50 μg<br>* Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).<br>|
| Experimental: Salmeterol 50 μg - placebo to indacaterol - indacaterol 300 μg<br>In treatment period 1, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); in treatment period 2, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); and in treatment period 3, patients received indacaterol 300 μg once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Salmeterol 50 μg<br>* Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Each Treatment Period (Day 15) | 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 each treatment period. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | After 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) 5 Minutes Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 5 minutes post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 15 Minutes Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 15 minutes post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 30 Minutes Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 30 minutes post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 1 Hour Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 1 hour post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 2 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 2 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 3 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 3 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 4 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 4 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 5 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 5 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 6 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 6 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 8 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 8 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 10 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 10 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 11 hours 10 minutes post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 11 hours 45 minutes post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 14 Hours Post-dose at the End of Each Treatment Period (Day 14) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 14 hours post-dose at the end of each treatment period (Day 14) | 
| Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 20 hours 10 minutes post-dose at the end of each treatment period (Day 15) | 
| Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 20 hours 45 minutes post-dose at the end of each treatment period (Day 15) | 
| Forced Expiratory Volume in 1 Second (FEV1) 22 Hours Post-dose at the End of Each Treatment Period (Day 15) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 22 hours post-dose at the end of each treatment period (Day 15) | 
| Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 23 hours 10 minutes post-dose at the end of each treatment period (Day 15) | 
| Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate. | 23 hours 45 minutes post-dose at the end of each treatment period (Day 15) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic obstructive pulmonary disease, COPD, indacaterol