A Randomized, Multicenter, Open-label, Parallel-group, 12-week Study to Assess the Efficacy and Safety of Switching From Tiotropium to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic Mild to Moderate COPD Patients

Study Overview
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Brief Summary
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To demonstrate superiority of QVA149 (110/50 μg) once daily compared to tiotropium 18 μg once daily in terms of trough forced expiratory volume in 1 second (FEV1) (mean of 45 min and 15 min pre-dose) following 12 weeks of treatment in mild to moderate symptomatic COPD patients

Official Title
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A Randomized, Multicenter, Open-label, Parallel-group, 12-week Study to Assess the Efficacy and Safety of Switching From Tiotropium to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic Mild to Moderate COPD Patients

Conditions
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COPD

Intervention / Treatment
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* Drug: Indacaterol and glycopyrronium (QVA149)
* Drug: Tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of COPD and post-bronchodilator FEV1 ≥ 50% of the predicted normal value and post-bronchodilator FEV1/FVC < 0.7 (COPD Grade 1 or 2 by severity of airflow limitation (GOLD 2015) Patients with CAT score ≥ 10 at Visit 0 and Visit 1. Patients who are on and have been on tiotropium monotherapy for the past 3 months. 0 or 1 COPD exacerbation in the previous 12 months (not leading to hospital admission). Exclusion Criteria: Treatment with any inhaled corticosteroid (ICS) in the 3 months prior to Visit 1. COPD exacerbation between Visit 0 and 1. Patients with concomitant pulmonary disease Patients with a history of respiratory infection within 4 weeks prior to Visit 0. Prior or current diagnosis of asthma. Presence of any contraindication, warning, precaution, hypersensitivity to LABA and LAMA 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: Indacaterol and glycopyrronium (QVA149)<br>QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Drug: Indacaterol and glycopyrronium (QVA149)<br>* Capsules for inhalation delivered via SDDPI<br>|
| Active Comparator: Tiotropium<br>Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks | Drug: Tiotropium<br>* Capsules for inhalation delivered via HandiHaler® device<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) After 12 Weeks of Treatment | Spirometry was performed according to internationally accepted standards. Trough FEV1 is defined as the mean of 45 minute and 15 minute pre-dose values. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of 45 minute and 15 minute pre-dose values. | mean of 45 min and 15 min pre-dose week 4 | 
| Baseline Transitional Dyspnea Index (TDI) Focal Score | A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. TDI captures changes from baseline, each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. | Week 12 | 
| Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Total score of COPD Assessment Test (CAT) will be measured at week 12. This questionnaire is completed by the patient. The score ranges from 0-40 where higher scores represent worse health status. Mild: Score = 0 - 10, Moderate: Score = 11 - 20, Severe: Score = 21 - 30, Very Severe: Score = 31 - 40. The CAT total score was the sum of 8 item scores (each ranging from 0 to 5). If 1 or 2 items were missing, they were replaced with the mean of the completed items. If 3 or more items were missing, the CAT total score was set missing | Week 12 | 
| Daily Rescue Medication Use (Number of Puffs) | The total number of puffs of rescue medication used over the last 24 hours will be recorded in the patient diary in the morning. The total number of puffs of rescue medication per day over the full 12 weeks will be calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient. The mean daily number of puffs of rescue medication used over 12 weeks will be summarized by treatments | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, open-label, QVA149, symptomatic, tiotropium