Study to Assess the Effect of Formoterol and Beclomethasone Dipropionate in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the effect of the combination of formoterol and beclometasone dipropionate on central and peripheral airway dimensions in COPD patients using Computational Fluid Dynamics (CFD). Further more, the effect of this combination therapy on lung function (spirometry, body plethysmography), the BODE index, COPD assessment test (CAT) and Borg CR10 scale will be assessed and the safety will be evaluated.

Official Title
-----------------
Open-label, Prospective Exploratory Study to Assess the Effects of Formoterol and Beclometasone Dipropionate Combination Therapy on Central and Peripheral Airway Dimensions in COPD Patients

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Inuvair


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with documented COPD based on the following criteria: Smoking history of at least 10 pack-years Decreased Tiffeneau index: FEV1/FVC < 0.70 Male or female patients aged ≥ 40 years Patients should be treated according to the 'Global initiative for chronic Obstructive Lung Disease' (GOLD) guidelines Patients who present Moderate COPD with an FEV1 between 50 and 80% of predicted GOLD 2) Severe COPD with an FEV1 between 30 and 50% of predicted (GOLD 3) Very severe COPD with an FEV1 lower than 30% of predicted (GOLD 4) Patients will be maintained on stable respiratory medications for 6 weeks prior to screening Patients with a co-operative attitude and ability to be trained to correctly use the pMDI Written informed consent obtained Exclusion Criteria: Pregnant or lactating females or females at risk of pregnancy Unstable patients who developed an exacerbation during the last 4 weeks Inability to carry out pulmonary function testing Diagnosis of asthma as defined by the current 'Global Initiative for Asthma' (GINA) guidelines Patients with an uncontrolled disease or any condition that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study Patients with a QTc interval (Bazett's formula) at the screening visit electrocardiogram (ECG) test >450 msec Cancer or any other chronic disease with poor prognosis and /or affecting patient status History of alcohol or drug abuse Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study Patients who received any investigational new drug within the last 4 weeks prior to the screening visit Patients treated with any non-permitted concomitant medication

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Inuvair<br> | Drug: Inuvair<br>* 6 µg formoterol and 100 µg beclometasone dipropionate combination spray pMDI aerosol<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral airway resistance (from 4th bifurcation on) for the segmented airways |  | at baseline and after 6 months of treatment | 
| Total airway volume for the segmented airways |  | at baseline and after 6 months of treatment | 
| Peripheral airway volume (from the 4th bifurcation on) for the segmented airways |  | at baseline and after 6 months of treatment | 
| Relative compliance for each lobe |  | at baseline and after 6 months of treatment | 
| Density of the lung parenchyma given per predefined lung zone |  | at baseline and after 6 months of treatment | 
| Total airway resistance for the segmented airways |  | at baseline and after 6 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BODE index | The BODE index is a multidimensional index of disease severity . The index uses following parameters: body mass index (BMI) degree of airflow obstruction (Forced Expiratory Volume in 1 second (FEV1): % of predicted) functional dyspnea (Modified Medical Reseach Council (MMRC) dyspnea scale) exercise capacity (6 minute walk distance (6MWD) - m) | at baseline (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment (visit 8) | 
| COPD assessment test | The COPD assessment measures the impact of COPD on a person's life. | at screening (visit 1), at baseline (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment (visit 8) | 
| Borg CR10 Scale | The Borg CR10 Scale measures the present dyspnea. | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Adverse events as a measure of safety | During the study patients will record record each day taken medication and any possible comments on the daily diary cards. Further more, patients are contacted at least once a month (either by phone or at a visit in the hospital). | during the study patients will record record each day taken medication and any possible comments on the daily diary cards | 
| Forced expiratory volume in 1 second (FEV1) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Forced Vital Capacity (FVC) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Peak Expiratory Flow (PEF) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Maximum expiratory flow rate at 50% of vital capacity (MEF50) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Maximal expiratory flow rate at 25% of vital capacity (MEF25) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Vital capacity (VC) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Inspiratory vital capacity (IVC) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Functional residual capacity (FRC) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Total Lung Capacity (TLC) |  | At screening, at baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Airway resistance (Raw) |  | At baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 
| Specific airways conductance (SGaw) |  | At baseline both pre and post dose (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment both pre and post dose (visit 8) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, Formoterol, Beclomethasone Dipropionate, Computational Fluid Dynamics, Functional Imaging, Central and Peripheral Airways, BODE index, COPD Assessment Test (CAT), Borg CR10 scale