Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Using Salmeterol as Active Control

Study Overview
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Brief Summary
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This study evaluated the safety and efficacy of 26 weeks treatment with indacaterol, placebo or salmeterol in patients with chronic obstructive pulmonary disease.

Official Title
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A 26-week Treatment, Multi-center, Randomized, Double-blind, Double- Dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, and Safety of Indacaterol (150 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease, Using Salmeterol (50 µg b.i.d.) as an Active Control

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: Clinical diagnosis of moderate to severe Chronic Obstructive Pulmonary Disease (COPD) as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006 Guidelines (mandatory) and including: Smoking history of at least 20 pack years Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% predicted and >or= 30% of predicted normal value Post-bronchodilator FEV1/FVC < 70% (Post defined as within 30 minutes of inhalation of 400 µg salbutamol) Exclusion Criteria: Pregnant or nursing (lactating) women and women of child-bearing potential UNLESS they meet pre-specified definitions of post-menopausal or are using pre-specified acceptable methods of contraception Hospitalisation for COPD exacerbation in the 6 weeks prior to Visit 1 or during run-in Patients requiring oxygen therapy for chronic hypoxemia (typically >15h/day) Respiratory tract infection within 6 weeks prior to Visit 1 and during the run-in period Concomitant pulmonary disease Asthma history (eosinophils > 400/mm3; symptoms prior to age 40). Includes history of childhood asthma History of long QTc syndrome or QTc interval > 450 ms for males and >470 ms for females Patients who have a clinically significant condition or a clinically relevant laboratory abnormality History of reactions to sympathomimetic amines or inhaled medication Inability to use the dry powder devices or perform spirometry Irregular day/night, wake/sleep cycles, e.g. shift workers Certain medications for COPD and allied conditions such as long acting bronchodilators must not be used prior to Visit 1 and for a pre-specified minimum washout period Patients unable or unwilling to complete a patient diary Other protocol-defined inclusion/exclusion criteria may apply.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol 150 μg<br>Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg<br>* Indacaterol 150 μg once daily (o.d) inhaled<br>Drug: Placebo to Salmeterol<br>* Placebo to salmeterol delivered via a proprietary dry powder inhaler<br>|
| Placebo Comparator: Placebo<br>Placebo to Indacaterol once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | Drug: Placebo to Indacaterol<br>* Placebo to Indacaterol inhaled via SDDPI.<br>Drug: Placebo to Salmeterol<br>* Placebo to salmeterol delivered via a proprietary dry powder inhaler<br>|
| Active Comparator: Salmeterol 50 μg<br>Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | Drug: Salmeterol 50 μg<br>* Salmeterol 50 μg twice daily (b.i.d) delivered via a proprietary dry powder inhaler<br>Drug: Placebo to Indacaterol<br>* Placebo to Indacaterol inhaled via 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) After 12 Weeks of Treatment | Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment | SGRQ is a health related quality of life questionnaire consisting of 76 items in three sections: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health status. The mixed model used baseline SGRQ total score, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates. | Week 12 | 
| Percentage of COPD Days of Poor Control During 26 Weeks of Treatment | Participants rated their symptoms on a scale of 0=none to 3=severe. A Chronic Obstructive Pulmonary Disease (COPD) day of poor control was defined as any day in the participants diary with a score >=2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). The mixed model used baseline percentage of days of poor control, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates. | Up to 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic obstructive pulmonary disease, indacaterol, salmeterol, placebo controlled