QVA149 Versus Fluticasone/Salmeterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety/tolerability of indacaterol and glycopyrronium (QVA149) (fixed-dose combination) with fluticasone/salmeterol over a 26-week period in patients with moderate to severe COPD.

Official Title
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A 26-week Treatment, Multi-center, Randomized, Doubleblind, Double Dummy, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of QVA149 Compared to Fluticasone/Salmeterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: indacaterol and glycopyrronium (QVA149)
* Drug: Placebo to fluticasone/salmeterol
* Drug: fluticasone/salmeterol
* Drug: Placebo to indacaterol and glycopyrronium (QVA149)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smoking history of at least 10 pack years Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease [GOLD] Guidelines, 2009) Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) >40% and < 80% of the predicted normal value and post-bronchodilator FEV1/Forced Vital Capacity (FVC) <70% Exclusion Criteria: Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the last year. Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia. Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1. Patients with concomitant pulmonary disease Patients with a history of asthma Any patient with lung cancer or a history of lung cancer (within last 5 years) Patients with a history of certain cardiovascular co-morbid conditions

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<br>Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol. | Drug: indacaterol and glycopyrronium (QVA149)<br>* QVA149 capsules delivered via dry powder inhaler (SDDPI), once daily.<br>Drug: Placebo to fluticasone/salmeterol<br>* Placebo to fluticasone/salmeterol delivered via Accuhaler® device, twice daily.<br>|
| Active Comparator: fluticasone/salmeterol<br>Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149). | Drug: fluticasone/salmeterol<br>* Fluticasone/salmeterol dry inhalation powder delivered via Accuhaler® device, twice daily.<br>Drug: Placebo to indacaterol and glycopyrronium (QVA149)<br>* Placebo to QVA149 delivered via dry powder inhaler (SDDPI), once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 | Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1 was normalized by 12 hours (divided by time). This outcome measures absolute values at week 26. Results are obtained from linear mixed model. | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 Hours | Standardized Forced Expiratory Volume in 1 Second (FEV1) was measured with spirometry conducted according to internationally accepted standards. Measurements were made between 0 and 12 hours after treatment. FEV1 was normalized by 12 hours (divided by time). This outcome measures absolute values at week 12. Results are obtained from linear mixed model. | Week 12 | 
| Forced Vital Capacity at All-time Points (Week 12) | Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function. This outcome measures absolute values at -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose week 12. Results are obtained from linear mixed model. | -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 12 | 
| Forced Vital Capacity at All-time Points (Week 26) | Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function. This outcome measures absolute values at -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 26. Results are obtained from linear mixed model. | -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 26 | 
| Focal Score of the Transitional Dyspnea Index (TDI) | Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement. | 12 weeks and 26 weeks | 
| Total Score of the St. George's Respiratory Questionnaire (SGRQ-C) | The total score of the St. George's Respiratory Questionnaire (SGRQ-C) is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. | 12 weeks and 26 weeks | 
| Mean Change From Baseline in Daily Number of Puffs of Rescue Medication | Participants maintained a diary to record the daily number of puffs of rescue medication used to treat COPD symptoms. | Baseline, 12 weeks and 26 weeks | 
| Change From Baseline in Symptom Scores Reported Using the Ediary | Participants maintained an ediary to record daily symptom scores (AM and PM) over 12 weeks and 26 weeks of treatment. This analysis compares the mean symptom scores over 12 weeks and 26 weeks compared to baseline. The diary records morning and evening daily clinical symptoms including cough, wheezing, shortness of breath, sputum volume, sputum purulence, night time awakenings and rescue medication use. Scale ranges: ranges are 0 to 3 with varying scale descriptions that pertain to the question being asked. 0 is the minimum score = none or No symptoms or never or No = mild, a little = moderate = severe For the scale range provided, high values represent a worse outcome. | 12 weeks and 26 weeks | 
| Inspiratory Capacity (IC) at All-time Points (12 Weeks) | After 12 weeks of treatment, Inspiratory Capacity (IC) was measured via spirometry, conducted according to internationally accepted standards. The mean of 3 acceptable measurements was calculated and reported in liters. | 12 weeks | 
| Inspiratory Capacity (IC) at All-time Points (26 Weeks) | After 26 weeks of treatment, Inspiratory Capacity (IC) was measured via spirometry, conducted according to internationally accepted standards. The mean of 3 acceptable measurements was calculated and reported in liters. | 26 weeks | 
| Number of Participants With Adverse Events | The assessment of safety was based on Adverse Events. A summary of adverse events is presented with this outcome, additional details are provided in Adverse Events Section. | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QVA149, indacaterol, NVA237, COPD, fluticasone/salmeterol