Study to Evaluate Efficacy/Safety of Combination Budesonide/Indacaterol vs Fluticasone/Salmeterol in Patients With COPD

Study Overview
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Brief Summary
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To demonstrate the free combination of budesonide and indacaterol is as efficacious as fluticasone and salmeterol in patients with COPD

Official Title
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24-week Study to Evaluate Efficacy and Safety of the Combination Budesonide / Indacaterol vs Fluticasone / Salmeterol in Patients With COPD

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Budesonide
* Drug: Fluticasone
* Drug: Indacaterol
* Drug: Salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed Outpatients with stable COPD groups C and D according to the 2011 GOLD Guidelines. Current or ex-smokers who have a smoking history of at least 10 pack years Patients with a history of at least one exacerbation. Patients able to read and complete Exclusion Criteria: Use of other investigational drugs within 30 days Patients with a history of hypersensitivity to any of the study drugs History or current diagnosis of ECG abnormalities Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range Patients who have not achieved an acceptable spirometry result at Visit 1 Patients with a body mass index (BMI) of more than 40 kg/m2 Patients with lung cancer or a history of lung cancer Patients with a history of malignancy of any organ system Pregnant or nursing (lactating) women Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers) Patients that are uncontrolled or unstable on permitted therapy, who in the opinion of the investigator, have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or haematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment Patients requiring oxygen therapy for chronic hypoxemia Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1 Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis, bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension Patients with a known diagnosis of Alpha-1 Antitrypsin deficiency. Patients with history of lung surgery Patients who are participating in the active phase of a supervised pulmonary rehabilitation program. Patients with a history of 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Budesonide/indacaterol<br>Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study. | Drug: Budesonide<br>* Budesonide 400 mcg twice a day via Breezhaler® device<br>Drug: Fluticasone<br>* Fluticasone 250 mcg twice daily via Accuhaler® device<br>Drug: Indacaterol<br>* Indacaterol 150 mcg once daily via Breezhaler® device<br>Drug: Salmeterol<br>* Salmeterol 50 mcg twice daily via Diskus® device<br>|
| Active Comparator: Fluticasone / salmeterol<br>Fixed combination of fluticasone and salmeterol | Drug: Fluticasone<br>* Fluticasone 250 mcg twice daily via Accuhaler® device<br>Drug: Salmeterol<br>* Salmeterol 50 mcg twice daily via Diskus® device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (Non-inferiority Analysis). | Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Health Status - mMRC | Modified Medical Research Council scale (mMRC) questionnaire will be completed by participants. 0 Not troubled with breathlessness except with strenuous exercise; 1 Troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3 Stops for breath after walking about 100 yards or after a few minutes on the level; 4 Too breathless to leave the house or breathless when dressing or undressing | Baseline, week 12 and week 24 | 
| Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Used Over the 24 Week Treatment | A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. | 24 weeks | 
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second at Week 24 (Analysis of Superiority) | Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. | Baseline and week 24 | 
| Change in Health Status - SGRQ-C | St George's Respiratory Questionnaire short version questionnaire will be completed by participants. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life) | Baseline, week 12 and week 24 |