A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease

Exclusion Criteria

• •Pregnant or lactating women and all women physiologically capable of becoming pregnant UNLESS they are willing to use highly effective birth control methods
• •Diagnosis of asthma or Asthma-COPD Overlap Syndrome (ACOS) as described in global initiative for asthma (GINA) Report 2016, history of allergic rhinitis or atopy (atopy which may raise contra-indications or impact the efficacy of the study treatment according to Investigator's judgment)
• •COPD Exacerbations: a moderate or severe COPD exacerbation that has not resolved ≤14 days prior to screening and ≤30 days following the last dose of any oral/systemic corticosteroid or antibiotic (whichever comes last). A Moderate or Severe COPD exacerbation during the run-in period
• •Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening or during run-in
• •Subjects treated with non-cardio-selective β-blockers in the month preceding screening or during the run-in period
• •Subjects treated with long-acting anti-histamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study, or if taken as needed
• •Subjects requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
• •Known respiratory disorders other than COPD which may impact the efficacy of the study treatment according the Investigator's judgment.
• •Subjects who have clinically significant cardiovascular condition
• •Subjects who have a clinically significant abnormal 12-lead ECG that results in active medical problem which may impact the safety of the subject according to Investigator's judgement
• •Subjects whose 12-lead ECG shows Fridericia corrected QT interval (QTcF) \>450 ms for males or QTcF \>470 ms for females at screening visit
• •Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would prevent use of anticholinergic agents
• •History of hypersensitivity to M3 receptor antagonists, β2-adrenergic receptor agonist, corticosteroids or any of the excipients contained in any of the formulations used in the study which may raise contra-indications or impact the efficacy of the study treatment according to the Investigator's judgement
• •Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study treatment according to Investigator's judgement
• •Subjects with serum potassium levels \<3.5 mEq/L (or 3.5 mmol/L) at screening
• •Use of potent cytochrome P450 2D6 and 3A4 inhibitors within 4 weeks prior to screening
• •Unstable or uncontrolled concurrent disease; fever, endocrine disease, gastrointestinal disease; neurological disease; hematological disease; autoimmune disorders, or other which may impact the feasibility of the results of the study according to Investigator's judgment
• •History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening
• •Subjects who have received an investigational drug within 1 month or 5 half-lives (whichever is greater) prior to screening visit, or have been previously randomized in this trial, or are currently participating in another clinical trial.
• •Subjects who are mentally or legally incapacitated, or subjects accommodated in an establishment as a result of an official or judicial order.
• •Subjects who have undergone major surgery in the 3 months prior to screening visit or have a planned surgery during the trial.