Comparison of Indacaterol 150 mcg Once Daily (o.d.) With Salmeterol/Fluticasone Propionate 50 mcg/500 mcg Twice Daily (b.i.d.)

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety of indacaterol with salmeterol /fluticasone propionate treatment in patients with moderate chronic obstructive pulmonary disease who, on entry to the study are being treated with salmeterol /fluticasone propionate.

Official Title
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A Randomized, Double-blind, Parallel-group, 26-week Study Comparing the Efficacy and Safety of Indacaterol (Onbrez® Breezhaler® 150 mcg o.d.) With Salmeterol/Fluticasone Propionate (Seretide® Accuhaler® 50 mcg/500 mcg b.i.d.) in Patients With Moderate Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with moderate COPD (Stage II) Able to perform spirometry assessments Current or ex-smokers On treatment with the fixed-dose combination of salmeterol 50 µg/fluticasone propionate 500 µg MDDPI b.i.d. for the treatment of COPD for ≥ 3 months directly preceding Visit 1. Exclusion Criteria: Having had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the past year. Having a history of, or current ECG abnormality Asthma 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol<br>Indacaterol 150 mcg once daily (o.d.) delivered via the Novartis single dose dry power inhaler (SDDPI) (Onbrez® Breezhaler®) | Drug: Indacaterol<br>* Indacaterol is delivered via a SDDPI.<br>|
| Active Comparator: Salmeterol/fluticasone propionate<br>Salmeterol 50 mcg /fluticasone propionate 500 mcg for inhalation delivered via a proprietary multi dose dry powder inhaler (MDDPI) device (Seretide® Accuhaler®) twice daily (b.i.d.) | Drug: Salmeterol<br>* Salmeterol/fluticasone is delivered via a MDDPI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in One Second (FEV1) at 12 Weeks (Imputed With LOCF): Treatment Comparisons | Spirometry conducted to internationally accepted standards. Trough FEV1 defined as the mean of the FEV1 measurements at 23 h 10 min and 23 h 45 min post the Day 84 morning dose. The primary variable (imputed with last observation carried forward) will be analysed using a mixed model for the Per Protocol Set (PPS). The model will contain treatment as a fixed effect with the baseline FEV1 measurement, FEV1 prior to inhalation and FEV1 10-15 min post inhalation of salbutamol (components of reversibility at Visit 1) as covariates. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough FEV1 (L) at Week 26 (Imputed With LOCF): Treatment Comparisons | Trough FEV1 is defined as the average of the 23 h 10 min and the 23 h 45 min values taken in the clinic at Visit 11. | 26 weeks | 
| FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group. | 12 weeks | 
| FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group . | 26 weeks | 
| FVC Over 26 Weeks of Treatment | FVC at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group. | 12 and 26 weeks | 
| Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison | The standardized (with respect to the length of time) AUC for FEV1 will be calculated between 5 min and 4 h post morning dose as the sum of trapezoids divided by the length of time at Day 84 (Visit 6) and Day 182 (Visit 10). Scheduled (not actual) time points are to be used. FEV1 measurements taken within 6 h of rescue use will be set to missing before the standardized AUC is calculated. | 12 and 26 weeks | 
| TDI Focal Score at Week 12 and Week 26: Treatment Comparisons | The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. | 12 and 26 weeks | 
| Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | The number of exacerbations during the 26 week treatment period will be analyzed using a generalized linear model assuming a negative binomial distribution. | 26 weeks | 
| Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | The mean daily number of puffs of rescue medication taken by the patient will be derived. If the number of puffs is missing for part of the day (either morning or evening) then a half day will be used in the denominator. Rescue medication data recorded during the 14 day run-in period will be used to calculate the baseline. The mean change from baseline in the daily number of puffs of rescue medication will be analyzed using the same mixed model as specified for the primary analysis, with the baseline FEV1 replaced with the baseline daily rescue use. | 12 and 26 weeks | 
| Rescue Medication Use Over 26 Weeks: Percentage of 'Days With no Rescue Use' | A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'. | 26 weeks | 
| St Georges Respiratory Questionnaire for COPD | A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present. | 12 and 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/fluticasone propionate