Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study was designed to provide pivotal confirmation of efficacy and safety data for 2 doses of indacaterol (150 and 300 µg once daily [od]) in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Data from this study will be used for the registration of indacaterol in Japan.

Official Title
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A 12-week Treatment, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol (150 and 300 µg Once Daily [od]) in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Indacaterol 150 μg capsules
* Drug: Indacaterol 300 μg capsules
* Drug: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of moderate-to-severe chronic obstructive pulmonary disease (COPD), as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 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 14 day run-in period prior to randomization. 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
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol 150 µg<br>Patients received indacaterol 150 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg capsules<br>* Indacaterol was supplied in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>|
| Experimental: Indacaterol 300 µg<br>Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM). 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 capsules<br>* Indacaterol was supplied in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>|
| Placebo Comparator: Placebo<br>Patients received placebo delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM). 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: Placebo capsules<br>* Placebo was supplied in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>|

What is the study measuring?
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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 Treatment (Week 12 + 1 Day, Day 85) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. | End of treatment (Week 12 + 1 day, Day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2 | 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 Week 2. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. | After Week 2 (Day 15) | 
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4 | 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 Week 4. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. | After Week 4 (Day 29) | 
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8 | 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 Week 8. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. | After Week 8 (Day 57) | 
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 (Day 84) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 50 and 15 minutes pre-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. | Prior to last dose at Week 12 (Day 84) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, chronic obstructive pulmonary disease, indacaterol, long acting β2-agonist