Assessment of Switching From Salmeterol/Fluticasone to Indacaterol/Glycopyrronium in a symtomaticCOPD Patient Cohort

Study Overview
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Brief Summary
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This study will investigate whether switching symptomatic COPD patients from a fixed-dose combination of salmeterol/fluticasone 50/500 µg b.i.d. to a fixed dose combination of QVA149 110/50 µg o.d. leads to improved lung function and airflow. It will also assess the effect on symptom burden, breathlessness, and use of rescue medication after this switch.

Official Title
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A 12-week Treatment, Multi-center, Randomized, Double-blind, Double-dummy, Parallel Group Study to Assess the Efficacy and Safety of Switching From Salmeterol/Fluticasone to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic COPD Patients

Conditions
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COPD

Intervention / Treatment
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* Drug: QVA149 110/50 micrograms
* Drug: Salmeterol/fluticasone 50/500 microgrammes


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. Male and female ≥ 40 years Current or ex-smokers who have a smoking history of at least 10 pack years (Ten pack years are defined as 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years). An ex-smoker is defined as a patient who has not smoked for ≥ 6 months at visit 1 Confirmed diagnosis of COPD and post-bronchodilator FEV1 ≥ 30% and < 80% of the predicted normal value and post-bronchodilator FEV1/FVC < 0.70 at visit 1 Treated with salmeterol/fluticasone 50/500 µg b.i.d. for at least 3 months prior to visit 1 Documented CAT score of ≥ 10 at Visit 1 and 2 Exclusion Criteria: Treatment with any LAMA in the 2 weeks prior to visit 1 Presence of any contraindication, warning, precaution, hypersensitivity in the approved prescribing information for salmeterol/fluticasone Prior or current diagnosis of asthma More than one COPD exacerbation requiring treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the year prior to Visit 1 Patients who developed a COPD exacerbation of any severity within the 6 weeks before the screening (Visit 1) or between screening (Visit 1) and start of treatment (Visit 2) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation Respiratory tract infection within 4 weeks prior to Visit 1 Respiratory tract infection between Visit 1 and 2. Patients can be re-screened 4 weeks after resolution of the infection Requiring oxygen therapy prescribed for >12 hours per day Onset of respiratory symptoms, including a COPD diagnosis prior to age 40 years

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: QVA149 110/50 micrograms<br>QVA149 110/50 micrograms o.d. Capsules for inhalation | Drug: QVA149 110/50 micrograms<br>* QVA149 110/50 micrograms o.d. capsules for inhalation, supplied in blisters via a single dose dry powder inhalater (SDDPI)<br>|
| Active Comparator: salmeterol/fluticasone 50/500 micrograms<br>salmeterol/fluticasone 50/500 micrograms b.i.d. Dry inhalation powder | Drug: Salmeterol/fluticasone 50/500 microgrammes<br>* Salmeterol/fluticasone 50/500 microgrammes b.i.d.dry inhalation powder delivered via Accuhaler / 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 Pre-dose FEV1 in Both Arms | Pulmonary function assessments were performed using centralized spirometry according to international standards. Mean trough pre-dose FEV1 at Week 12 is defined as the average of the measurements taken -45min and -15min pre study medication dose in the clinic after 12 weeks of treatment (Day 84). The baseline measurement is defined as the average of the scheduled FEV1 values prior to first intake of randomized study drug at Day 1 (Visit 2). | Baseline, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transitional Dyspnea Index (TDI) Focal Score | Transition Dyspnea Index (TDI) is an instrument used to assess a participant's level of dyspnea. The TDI focal score have three domains: functional impairment, magnitude of task and magnitude of effort. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline. | Baseline, week 12 | 
| Change From Baseline in FVC (Forced Vital Capacity) | Pulmonary function assessments were performed using centralized spirometry according to international standards. FVC wil follow the same analysis as for FEV1 | week 12 | 
| Change From Baseline in Total Symptom Score- CAT (COPD Assessment Test) | The participants will record their COPD symptoms in this test before every clinic visit, this will include : cough, phlegm, chest tightness, breathlessness, limitation in activities, energy, soundly sleep, etc. A higher score indicates a worse health status. The result is immediately available without the need for any calculation, apart from summing the scores on individual items. Scores of 0 - 10 represent mild, 11 - 20 represent moderate, 21 - 30 represent severe and 31 - 40 represent very severe clinical impact of COPD upon the patient. | week 12 | 
| Change From Baseline in Mean Daily Use of Rescue Medication | Use of rescue medication (number of puffs taken in the previous 12 hours) is recorded morning and evening, by the patient, in a paper diary. A negative change from baseline indicates an improvement. | over 12 weeks |