Efficacy and Safety of QVA149 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of QVA149 in patients with moderate to severe COPD.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Multicentre Study to Determine the Effect of QVA149 on Lung Function in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: indacaterol/glycopyrrolate
* Drug: indacaterol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure. Patients with moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD) according to the Global Initiative for Obstructive Lung Disease (GOLD) Guidelines 2006. Patients who have smoking history of at least 10 pack years. Patients with a post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) ≥30% and < 80% of the predicted normal and post-bronchodilator FEV1/Forced Vital Capacity (FVC) <0.70. Exclusion Criteria: Pregnant or nursing women, or women of child-bearing potential, regardless of whether or not sexually active if they are not using acceptable methods of contraception. Patients requiring long term oxygen therapy (> 15 hours a day) on a daily basis for chronic hypoxemia, or who have been hospitalized or visited an emergency department for a COPD exacerbation or as result of their airways disease in the 6 weeks prior to screening. Patients who have had a respiratory tract infection within 6 weeks prior to screening. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis. Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count > 400/mm3. Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition. Patients with uncontrolled Type I and Type II diabetes. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years. Patients who are contraindicated for or who have shown an untoward reaction to inhaled anticholinergic agents. Patients with a history of long QT syndrome or whose QTc interval (Fridericia method) measured at screening is prolonged (>450 ms for males or >470 ms for females). Patients with a history of untoward reactions to sympathomimetic amines, inhaled medication or any component thereof, or any of the study drugs or drugs with similar chemical structures. 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: indacaterol/glycopyrrolate 300/50 μg<br>One indacaterol/glycopyrrolate 300/50 μg capsule + 1 placebo capsule inhaled once daily via a single dose dry powder inhaler for 7 days. | Drug: indacaterol/glycopyrrolate<br>* Inhalation capsule indacaterol/glycopyrrolate 300/50 μg inhaled once daily via a single dose dry powder inhaler for 7 days.<br>* Other names: QVA149;|
| Active Comparator: indacaterol 600 μg<br>Two indacaterol 300 μg capsules inhaled once daily via a single dose dry powder inhaler for 7 days. | Drug: indacaterol<br>* Inhalation capsule indacaterol supplied as 300 μg capsules inhaled once daily via a single dose dry powder inhaler for 7 days.<br>* Other names: QAB149;|
| Active Comparator: indacaterol 300 μg<br>One capsule indacaterol 300 μg + one placebo capsule inhaled once daily via a single dose dry powder inhaler for 7 days. | Drug: indacaterol<br>* Inhalation capsule indacaterol supplied as 300 μg capsules inhaled once daily via a single dose dry powder inhaler for 7 days.<br>* Other names: QAB149;|
| Placebo Comparator: placebo<br>Two placebo capsules inhaled once daily via a single dose dry powder inhaler for 7 days. | Drug: placebo<br>* Placebo inhalation capsules inhaled once daily via a single dose dry powder inhaler for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 7 | Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute measurements post dosing. Baseline FEV1 is the mean of the 45 minute and 15 minute pre-dose FEV1 values at day 1 of each period. Least square means are based on the Analysis of Covariance Trough FEV1 at day 7 = sequence effect + patient(sequence) + period effect + treatment effect + (period) baseline FEV1 + error. | Baseline, Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve (AUC) 5 Minutes-12 Hours at Day 7 | Spirometry testing was performed in accordance with American Thoracic Society standards. FEV1 was assessed at 5, 15, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on Day 7. Standardized (with respect to time) AUC (5 minutes-12 hours) for FEV1 on day 7 was calculated using the trapezoidal rule. Least square means are based on the Analysis of Covariance: FEV1 AUC = sequence effect + patient (sequence) + period + treatment + baseline FEV1 (period) + error. | Day 7 | 
| Number of Participants With Adverse Events, Serious Adverse Events and Discontinuations Due to Adverse Events | Additional information about adverse events can be found in the Adverse Event Section. | 47 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QVA, Indacaterol, Glycopyrrolate, Concept1, COPD, cross over study, safety and efficacy, trough FEV1