Effect of QVA149 on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study assessed the effect of once-daily indacaterol and glycopyrronium bromide (QVA149) on exercise endurance in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Official Title
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A Randomized, Blinded, Double Dummy, Multi-center, Placebo Controlled, 3 Period, Crossover Study to Assess the Effect of QVA149 (110/50 µg o.d.) on Exercise Endurance in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control.

Conditions
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COPD

Intervention / Treatment
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* Drug: indacaterol and glycopyrronium bromide (QVA149)
* Drug: placebo
* Drug: tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD) stage II or stage III according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines (2009) Qualifying spirometry, Forced Expiratory Volume in one second (FEV1) and post-bronchodilator FEV1/FVC (Forced Vital capacity) Smoking history ≥ 10 pack years Exclusion Criteria: Pregnant women or nursing mothers or women of child-bearing potential not using adequate contraception Cardiac abnormality History of asthma Contraindications to cardiopulmonary exercise testing Participation in active phase of pulmonary rehabilitation program History of cancer within the past 5 years 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: indacaterol and glycopyrronium bromide (QVA149)<br>QVA149 delivered once daily via single-dose dry powder inhaler. | Drug: indacaterol and glycopyrronium bromide (QVA149)<br> <br> |
| Placebo Comparator: placebo<br>Placebo, delivered once daily via single-dose dry powder inhaler. | Drug: placebo<br> <br> |
| Active Comparator: tiotropium<br>Tiotropium delivered once daily via HandiHaler® device. | Drug: tiotropium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Tolerance Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured by exercise endurance time (in seconds) during a sub-maximal constant load cycle ergometry test ((SMETT)which is a cycle exercise test) after three weeks of treatment. | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dynamic Inspiratory Capacity Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using dynamic inspiratory capacity at isotime during sub-maximal constant load cycle ergometry test ((SMETT)a cycle exercise test), after three weeks of treatment. | 3 weeks | 
| Trough 24 Hour Post Dose Inspiratory Capacity Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using trough 24 hour post dose inspiratory capacity after three weeks of treatment. | 3 weeks | 
| Trough 24 Hour Post Dose Forced Expiratory Volume in One Second Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using trough 24 hour post dose Forced Expiratory Volume in one second (FEV1) after three weeks of treatment. | 3 weeks | 
| Pulmonary Function Test Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Slow Vital Capacity (SVC) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography. | day 1 and day 21 | 
| Pulmonary Function Test (RV) Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Residual Volume (RV) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography. | day 1 and day 21 | 
| Pulmonary Function Test (SGaw) Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Specific Airway Conductance (SGaw) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography. | day 1 and day 21 | 
| Pulmonary Function Test (FRC) Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using the pulmonary function test for Functional Residual Capacity (FRC) on day 1 and day 21, at 5 min and 15 min post dose as determined by body plethysmography. | day 1 and day 21 | 
| Spirometry After Three Weeks of Treatment on Patients Not Exercising | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using dynamic inspiratory capacity post-dose pre-exercise after three weeks of treatment. | 3 weeks | 
| Exertional Dyspnea Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured using exertional dyspnea Borg CR10 Scale® (After 3 weeks of treatment, before, during and after exercise, patients were asked to rate the intensity of their breathing and leg discomfort using the Borg CR10 Scale®). This scale consists of 12-point score that the participants pointed to so as to indicate their level of dyspnea before and during exercise testing (where 0 indicates no breathlessness at all and 12 indicates maximum breathlessness). A reduction in this score indicates an improvement. | 3 weeks | 
| Leg Discomfort During Exercise Comparison Between QVA149 and Placebo Groups | The effect of indacaterol and glycopyrronium bromide (QVA149) compared to placebo on leg discomfort was measured using Borg CR10 Scale® during sub-maximal constant load cycle ergometry test after three weeks treatment. | 3 weeks | 
| Exercise Endurance Comparison Between QVA149 and Tiotropium Groups | Effect of QVA149 110/50 µg o.d. compared with tiotropium 18 µg o.d. in patients with moderate to severe COPD with respect to exercise endurance was measured by a sub-maximal constant load cycle ergometry test ((SMETT)cycle exercise test) after three weeks of treatment. | 3 weeks | 
| Exercise Endurance Time Comparison After a Single Dose of QVA149 Versus Placebo | The effect of a single dose of indacaterol and glycopyrronium bromide (QVA149) compared to placebo was measured with respect to exercise endurance time during sub-maximal constant load cycle ergometry test ((SMETT)cycle exercise test). | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, QVA149, tiotropium, exercise, exercise tolerance, combination bronchodilator, moderate to severe COPD