A Phase II, 5-way Cross-over Study to Evaluate the Pharmacodynamics of "Nexthaler" Dry Powder Inhaler in COPD Patients

Phase II, Partial Blind, Randomized, Placebo Controlled, 5-way Cross-over Study to Evaluate the Pharmacodynamics of BDP(Beclomethasone Diproprionate)/B17MP (Beclomethasone-17-Monoproprionate) and FORMOTEROL FUMARATE (FF) Across Two Different Dose Levels of CHF 1535 NEXThaler DPI (Dry Powder Inhaler) and CHF 1535 pMDI (Pressurized Metered-dose Inhaler)in Adult COPD (Chronic Obstructive Pumonary Disease) Patients

The study aim is to compare the pharmacodynamic effects (cardiovascular effects- primary variable: Heart rate over 4 hours post dosing- ) after administration of BDP and formoterol administered as CHF 1535 100/6 NEXThaler DPI or CHF1535 pMDI at two different dose levels.

The effects of both formulations on serum potassium and serum glucose and the general safety and tolerability of study treatments will be also evaluated

Inclusion Criteria:

• Male and female adults (≥ 40 and ≤ 75 years old).
• Outpatients with diagnosis of moderate/severe stable COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines update 2013 at least in the 6 months before the screening visit.
• A post-bronchodilator FEV1(Forced Expiratory Volume in one second) ≥ 40 and < 80% of the predicted normal value and FEV1/FVC (Forced Vital Capacity) < 0.7, after 4 puffs (4 x 100 µg) of salbutamol pMDI. If this criterion is not met at screening, the test can be repeated once before commencing of the run-in period.
• Ability to use pMDI (pressured metered-dose inhaler)and DPI (dry powder Inhaler) devices
• Current or past smoker of at least 10 pack/years where one pack-year is equivalent to 20 cigarettes per day for 1 year

Exclusion Criteria:

• Pregnant or lactating female subjects.

• Current diagnosis of Asthma (as defined by the current GINA (Global Initiative for Asthma guidelines 2012 (update), or history of allergic rhinitis.

• COPD exacerbations requiring systemic steroids and /or antibiotics and/or oral or nebulized beta 2-agonists in the 4 weeks prior to screening and until randomization.

• Lower Respiratory Tract Infection (LRTI) in the 4 weeks prior to screening and until randomization.

• Patients with serum potassium levels < 3.5 mEq/L (milliequivalent per liter).

• History of substance abuse or drug abuse within 12 months prior to screening visit.

• Known respiratory disorders other than COPD including but not limited to α1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, restrictive lung disease and interstitial lung disease.

• Intolerance or contra-indication to treatment with beta 2-agonists and/or inhaled corticosteroids or allergy to any component of the study treatments.

• Patients treated with non-cardioselective β-blockers in the month preceding the screening visit or during the study period.

• Patients who have clinically significant cardiovascular disease according to investigator's judgement. Thus includes but is not limited to:

  • congestive heart failure (NYHA class > 3);
  • acute ischemic heart disease within the past 12 months of screening;
  • Sustained cardiac arrhythmias (supraventricular or ventricular, >30 seconds duration) at or within 6 months of screening;
  • Non sustained cardiac arrhythmias (supraventricular or ventricular, > 3 beats < 30 seconds and or ending spontaneously and or asymptomatic);
  • History of sustained and non-sustained cardiac arrhythmias (supraventricular or ventricular);
  • 2nd or 3rd degree Atrioventricular conduction block;
  • Left Bundle Branch Block.

• An abnormal 12-lead ECG (QRS> 120 msec, PR> 220 msec, HR < 40 bpm, Heart Rate > 110 bpm) at screening or at randomization.

• Patients whose electrocardiogram (12-lead ECG) shows QTcF >450 ms for males or QTcF > 470 ms for females at screening or at randomisation.

• Patients whose DBP/SBP is higher than: DBP 90 mmHg or SBP 160 mmHg at screening or at randomization.