Effect of QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) on Cardiac Function in COPD Patients

Study Overview
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Brief Summary
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This mechanistic study is a single-center, randomized, double-blind, placebo-controlled, cross-over study to evaluate the effect of dual bronchodilation with QVA149 on cardiac and lung function parameters in hyperinflated COPD patients.

Official Title
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A Randomized, Double-blinded, Single-center, Placebo Controlled, Cross-over Study to Assess the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) on Cardiac 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: QVA149
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with airflow limitation indicated by a post-bronchodilator FEV1 <80% of the predicted normal value and a post-bronchodilator FEV1/FVC<0.7 Current or ex-smokers who have a smoking history of at least 10 pack years. Able and willing to give written informed consent Hyperinflated patients with RVol>135% predicted Exclusion Criteria: Patients on LABA or LAMA treatment at Visit 1. History of one COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization 3 months prior to Visit 2. More than one COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization within 6 months prior to Visit 2. Patients who have clinically significant cardiovascular abnormalities, which could interfere with the assessment of the study treatment (such as but not limited to cardiac arrhythmias, heart failure with left ventricular ejection fraction <40% as determined by MRI scan, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, history of myocardial infarction 6 months prior to Visit 2) Patients with a known history or current atrial fibrillation to be confirmed by ECG. Patients with pacemaker, bypass or stent. Patients whose QTcF measured at Visit 3 is >450 ms for males and >470 ms for females Additional study-specific inclusion and 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: Treatment sequence 1<br>QVA149 from day 1 to day 15 followed by Placebo from day 29 to day 43 | Drug: QVA149<br>* QVA149 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily<br>* Other names: Ultibro;Drug: Placebo<br>* Placebo to QVA140 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily<br>|
| Experimental: Treatment sequence 2<br>Placebo from day 1 to day 15 followed by QVA149 from day 29 to day 43 | Drug: QVA149<br>* QVA149 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily<br>* Other names: Ultibro;Drug: Placebo<br>* Placebo to QVA140 capsules 100/50 µg for inhalation via Concept-1-inhaler, taken once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular End-diastolic Volume (LVEDV) | Left ventricular enddiastolic volume (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the chamber's filling with blood and will be determined as measured by MRI. | Baseline, week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Forced Expiratory Volume in One Second (FEV1). | Forced Expiratory Volume in one second (FEV1) will be calculated as the volume of air forcibly exhaled in one second as measured by spirometry. | Baseline, week 2 | 
| Change in Forced Vital Capacity (FVC). | Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry. | Baseline, week 2 | 
| Change in Inspiratory Capacity (IC) at Each Time-point | Inspiratory capacity (IC) was defined as the mean of the maximum IC over 3 values measured by bodyplethysmography according to internationally accepted standards. | Baseline, week 2 | 
| Change in Total Lung Capacity (TLC) | Total Lung Capacity (TLC) will be calculated from the mean Functional Residual Capacity (FRC) plus the highest value of the Inspiratory Capacity, both measured by body plethymography according to internationally accepted standards. | Baseline, week 2 | 
| Change in Residual Volume (RVol) | Residual Volume (RVol) will be calculated from the value of Total Lung Capacity (TLC) minus the highest value of the Slow Vital Capacity, both measured by body plethymography according to internationally accepted standards. | Baseline, week 2 | 
| Change in Specific Airway Resistance (sRaw) | Specific Airway Resistance (sRaw) will be documented as effective resistance (sReff) calculated as the median of five acceptable measurements. Values will be measured by body plethymography according to internationally accepted standards. | Baseline, week 2 | 
| Change in Functional Residual Capacity (FRC) | Functional Residual Capacity (FRC) will be calculated as the mean of three reproducible values as measured by body plethymography according to internationally accepted standards. | Baseline, week 2 | 
| Change in Right Ventricular (RV) and Left Ventricular (LV) Ejection Fraction (EF) | Right and left ventricular ejection fraction is the fraction of blood (in percent) pumped out of the heart's left and right ventricular chamber, respectively, with each heart beat and will be determined as measured by MRI. | Baseline, week 2 | 
| Change in Left and Right Ventricular End-systolic Volume | Right ventricular end-systolic volume (RV-ESV) and left ventricular end-systolic volume (LV-ESV) is a measurement of the volume of blood in the heart's right and left ventricular chamber, respectively, at the end of the heart's contraction and will be determined as measured by MRI. | Baseline, week 2 | 
| Change in Right Ventricular Enddiastolic Volume | Right ventricular end-diastolic volume is a measurement of the volume of blood in the heart's right ventricular chamber at the end of the chamber's filling with blood and will be determined as measured by MRI. | Baseline, week 2 | 
| Cardiac Output at Each Time-point, Left and Right Ventricular Cardiac Output (LVCO and RVCO) | Cardiac output is calculated as the heart rate multiplied by the stroke volume (= difference between ventricular enddiastolic volume and endsystolic volume) that will be determined as measured by MRI. | week 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QVA149, cardiac function, ventricular enddiastolic volume, hyperinflated COPD patients