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

• Peripheral airway resistance (from 4th bifurcation on) for the segmented airways [ Time Frame: at baseline and after 6 months of treatment ] [ Designated as safety issue: No ]
• Total airway volume for the segmented airways [ Time Frame: at baseline and after 6 months of treatment ] [ Designated as safety issue: No ]
• Peripheral airway volume (from the 4th bifurcation on) for the segmented airways [ Time Frame: at baseline and after 6 months of treatment ] [ Designated as safety issue: No ]
• Relative compliance for each lobe [ Time Frame: at baseline and after 6 months of treatment ] [ Designated as safety issue: No ]
• Density of the lung parenchyma given per predefined lung zone [ Time Frame: at baseline and after 6 months of treatment ] [ Designated as safety issue: No ]
• Total airway resistance for the segmented airways [ Time Frame: at baseline and after 6 months of treatment ] [ Designated as safety issue: No ]

• Peripheral airway resistance (from 4th bifurcation on) for the segmented airways [ Designated as safety issue: No ]
• Total airway volume for the segmented airways [ Designated as safety issue: No ]
• Peripheral airway volume (from the 4th bifurcation on) for the segmented airways [ Designated as safety issue: No ]
• Relative compliance for each lobe [ Designated as safety issue: No ]
• Density of the lung parenchyma given per predefined lung zone [ Designated as safety issue: No ]
• Total airway resistance for the segmented airways [ Designated as safety issue: No ]

• BODE index [ Time Frame: at baseline (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment (visit 8) ] [ Designated as safety issue: No ]

  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)
• COPD assessment test [ Time Frame: at screening (visit 1), at baseline (visit 2), after 3 months of treatment (visit 5) and after 6 months of treatment (visit 8) ] [ Designated as safety issue: No ]
  The COPD assessment measures the impact of COPD on a person's life.
• Borg CR10 Scale [ Time Frame: 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) ] [ Designated as safety issue: No ]
  The Borg CR10 Scale measures the present dyspnea.
• Adverse events as a measure of safety [ Time Frame: during the study patients will record record each day taken medication and any possible comments on the daily diary cards ] [ Designated as safety issue: Yes ]
  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).
• Forced expiratory volume in 1 second (FEV1) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Forced Vital Capacity (FVC) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Peak Expiratory Flow (PEF) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Maximum expiratory flow rate at 50% of vital capacity (MEF50) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Maximal expiratory flow rate at 25% of vital capacity (MEF25) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Vital capacity (VC) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Inspiratory vital capacity (IVC) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Functional residual capacity (FRC) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Total Lung Capacity (TLC) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Airway resistance (Raw) [ Time Frame: 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) ] [ Designated as safety issue: No ]
• Specific airways conductance (SGaw) [ Time Frame: 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) ] [ Designated as safety issue: No ]

• BODE index [ Designated as safety issue: No ]

  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)
• COPD assessment test [ Designated as safety issue: No ]
  The COPD assessment measures the impact of COPD on a person's life.
• Borg CR10 Scale [ Designated as safety issue: No ]
  The Borg CR10 Scale measures the present dyspnea.
• Adverse events as a measure of safety [ Designated as safety issue: Yes ]
• Forced expiratory volume in 1 second (FEV1) [ Designated as safety issue: No ]
• Forced Vital Capacity (FVC) [ Designated as safety issue: No ]
• Peak Expiratory Flow (PEF) [ Designated as safety issue: No ]
• Maximum expiratory flow rate at 50% of vital capacity (MEF50) [ Designated as safety issue: No ]
• Maximal expiratory flow rate at 25% of vital capacity (MEF25) [ Designated as safety issue: No ]
• Vital capacity (VC) [ Designated as safety issue: No ]
• Inspiratory vital capacity (IVC) [ Designated as safety issue: No ]
• Functional residual capacity (FRC) [ Designated as safety issue: No ]
• Total Lung Capacity (TLC) [ Designated as safety issue: No ]
• Airway resistance (Raw) [ Designated as safety issue: No ]
• Specific airways conductance (SGaw) [ Designated as safety issue: No ]

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.

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