Safety and Efficacy of Indacaterol Once Daily Versus Salmeterol Twice Daily in Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study compared the safety and efficacy of indacaterol 150 µg taken once daily (o.d.) versus salmeterol 50 µg taken twice daily (b.i.d) in patients 40 years old or older with chronic obstructive pulmonary disease.

Official Title
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A 12 Week Treatment, Multi-center, Randomized, Parallel Group, Double Blind, Double Dummy Study to Assess the Superiority of Indacaterol (150 µg o.d.) Via a SDDPI in Patients With Moderate to Severe COPD, Using Salmeterol (50 µg b.i.d.) as an Active Comparator Delivered Via a DISKUS Inhaler

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Indacaterol 150 µg
* Drug: Salmeterol 50 µg
* Drug: Placebo to indacaterol
* Drug: Placebo to salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged ≥ 40 years Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the GOLD Guidelines, 2007) and: Smoking history of at least 10 pack years Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% of the predicted normal value at screening Post-bronchodilator FEV1/FVC (forced vital capacity) < 70% at screening Exclusion Criteria: Patients who have received systemic corticosteroids for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period Patients requiring long-term oxygen therapy (> 15 h 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 (Fridericia's) measured at screening 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 inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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<br>* Indacaterol 150 μg was provided in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).<br>Drug: Placebo to salmeterol<br>* Placebo to salmeterol was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]).<br>|
| Active Comparator: Salmeterol 50 µg<br>Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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: Salmeterol 50 µg<br>* Salmeterol 50 μg was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]).<br>Drug: Placebo to indacaterol<br>* Placebo to indacaterol was provided 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 |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; 1, 2, 3, 4, and 8 hours; 11 hours 10 minutes and 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates. | From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates. | 24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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respiratory, dyspnea, breathlessness, COPD, indacaterol, long-acting β2-agonist