Randomized, Double-blind, Placebo-controlled, Multicenter, Cross-over Study to Assess the Effects of a 3 Week Therapy Each With QVA149 Versus Placebo on Pulmonary Function and Average Physical Activity Levels in Patients With COPD.

Study Overview
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Brief Summary
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This study is designed to assess the effect of QVA149 (110/50 ug q.d.) versus placebo on pulmonary function and average physical activity levels in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Official Title
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MOVE - A Randomized, Double-blind, Placebo-controlled, Multicenter, Cross-over Study to Assess the Effects of a 3 Week Therapy Each With QVA149 Versus Placebo on Pulmonary Function and Average Physical Activity Levels in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: QVA149
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with stable COPD according to the current GOLD guidelines (GOLD 2013). Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack /day x 10 yrs, or ½ pack/day x 20 yrs).. Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥40% and <80% of the predicted normal, and a post-bronchodilator FEV1/FVC <0.70 Exclusion Criteria: Patients with conditions contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof, anticholinergics, long and short acting beta2 agonists, sympathomimetic amines, lactose or any of the other excipients Patients who have a clinically significant ECG abnormality at Visit 1, who in the judgment of the investigator would be at potential risk if enrolled into the study. Patients with paroxysmal (e.g. intermittent) atrial fibrillation are excluded. Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, atrial fibrillation must be present at baseline and screening visits, with a resting ventricular rate < 100/min. Patients with Type I or uncontrolled Type II diabetes and patients with a history of blood glucose levels consistently outside the normal range Patients with narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with non-melanoma skin carcinoma may be considered for the study. Patients with a body mass index (BMI) of more than 40 kg/m2. Women who are pregnant or breast feeding Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia. Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening. Patients who have had a respiratory tract infection within 4 weeks prior to screening. Patients with any history of asthma. Patients with concomitant pulmonary disease Patients with clinically significant bronchiectasis. 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment sequence I<br>QVA149 once a day during 21 days cross-over to placebo once a day for up to 21 days | Drug: QVA149<br>* QVA149 (110/50 µg) once a day via Breezhaler® device<br>Drug: Placebo<br>* Placebo once a day via Breezhaler® device<br>|
| Active Comparator: Treatment sequence II<br>Placebo once a day during 21 days cross-over to QVA149 once a day for 21 days | Drug: QVA149<br>* QVA149 (110/50 µg) once a day via Breezhaler® device<br>Drug: Placebo<br>* Placebo once a day via Breezhaler® device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Peak Inspiratory Capacity (IC) Comparison Between QVA149 and Placebo | Inspiratory capacity (IC) will be measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the IC measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36 | Baseline, day 22, baseline day 36, day 57 | 
| Change From Baseline in the Comparison of QVA149 Versus Placebo With Respect to Average Physical Activity Level | Average physical activity level is defined by average daily activity-related energy consumption [Kcal/day], measured via Actinography device. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the activity measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36 | Baseline, day 22, baseline day 36, day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Comparison of QVA149 vs. Placebo on the Average Number of Steps Per Day | The average number of steps per day will be measured via Actinography device. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the activity measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day 1 or Day 57-Day36 | Baseline, day 22, baseline day 36, day 57 | 
| Change in the Duration of at Least Moderate Activity Per Day Comparison of QVA149 Versus Placebo | Least moderate activity (defined as 3,5-7kcal/min) will be measured via Actinography device. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the activity measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36 | Baseline, day 22, baseline day 36, day 57 | 
| Change From Baseline in Peak IC Comparison Between QVA149 and Placebo on Day 1. | Inspiratory capacity (IC) will be measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. The IC measurements collected prior to dosing on either Day 1 or 36, respectively, were subtracted from the appropriate peak measures on the same respective days | Day 1 or day 36 | 
| Change From Baseline in the Trough IC Comparison Between QVA149 and Placebo | Inspiratory capacity (IC) will be measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the IC measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36 | Baseline, day 22, baseline day 36, day 57 | 
| Peak Forced Expiratory Volume 1 (FEV1) Comparison Between QVA149 and Placebo at Day 1 | 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. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. The FEV1 measurements collected prior to dosing on either Day 1 or 36, respectively, were subtracted from the appropriate peak measures on the same respective days | Day 1 or day 36 | 
| Trough FEV1 Comparison Between QVA149 and Placebo After 22 Days | 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. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the FEV1 measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36 | Baseline, day 22, baseline day 36, day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic obstructive pulmonary disease, COPD