Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control

Study Overview
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Brief Summary
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This study was designed to assess the efficacy and long-term safety of 300 and 600 µg doses of indacaterol when delivered via a single-dose dry-powder inhaler (SDDPI) in patients with chronic obstructive pulmonary disease (COPD). Patients were randomized to receive either indacaterol 300 µg once daily, indacaterol 600 µg once daily, formoterol 12 µg twice daily, or placebo.

Official Title
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A 52-week Treatment, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol (300 and 600 µg Once Daily) in Patients With Chronic Obstructive Pulmonary Disease, Using Formoterol (12 µg Twice Daily) as an Active Control

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Formoterol
* Drug: Placebo to indacaterol
* Drug: Placebo to formoterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults ≥ 40 years, with a diagnosis of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2005 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 volume capacity) < 70% (Post refers to within 30 minutes after inhalation of 400 μg of salbutamol) Exclusion Criteria: Patients who were hospitalized for a COPD exacerbation in the 6 weeks prior to screening. Patients who 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. Patients with a history of certain cardiovascular co-morbid conditions. 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 300 μg plus placebo to formoterol<br>Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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<br>* Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to formoterol<br>* Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).<br>|
| Experimental: Indacaterol 600 μg plus placebo to formoterol<br>Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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<br>* Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to formoterol<br>* Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).<br>|
| Active Comparator: Formoterol 12 μg plus placebo to indacaterol<br>Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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: Formoterol<br>* Formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>|
| Placebo Comparator: Placebo to indacaterol plus placebo to formoterol<br>Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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 to indacaterol<br>* Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to formoterol<br>* Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).<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) at 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/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. | Week 12 + 1 day, Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Days of Poor Control During 52 Weeks of Treatment | Percentage of days of poor control was defined as the number of days in the patient diary with a score ≥ 2 (scale of 0-3, a higher number means more severe symptoms) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness) over 52 weeks divided by the number of evaluable days (days with ≥ 2 symptoms with scores). The analysis included baseline percentage of days of poor control, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. | Baseline to end of study (Week 52) | 

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