A 24-wk Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of a New PDE4 Inhibitor in Patients With COPD

A 24-week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo and Active Controlled, Parallel Group, Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF6001 DPI in Patients With COPD on a Background Therapy

The purpose of this study is to evaluate the dose-response relationship of different doses of CHF6001 and to identify the optimal dose (s) in terms of benefit/risk ratio for further development in the target patient population.

This is a phase II, randomized, double-blind, double-dummy, placebo and active controlled multinational, multicenter, dose ranging, 6-arm parallel-group study to identify the optimal dose of CHF6001, PDE4 inhibitor under development, with respect to lung functions and symptoms.

After a 2-wk run-in period under formoterol (Oxis Turbohaler®) and rescue salbutamol prn, patients will be randomized to one of the 6 treatment groups. After the randomization, patients will be assessed after 3, 6, 12, 18 and 24 weeks of treatment at clinic/hospital. A follow-up visit will be performed 12 days after the last visit.

During the study, patients will report daily symptoms with the EXACT-PRO/E-RS questionnaire, rescue/background medication use and compliance with the study medications. AEs, SAEs and COPD exacerbations will be monitored throughout the study. At randomization and subsequent visits, patients will undergo physical and vital signs examinations, spirometry measurement, 12-lead ECG. Symptoms and Health status will be assessed through validated questionnaires. Routine lab analysis and blood biomarkers will be done.

Inclusion Criteria:

• COPD patients
• Non- childbearing potential or woman permanently sterilized or on one or more highly effective contraception
• Current/ex smokers (history > 10 pack years)
• Post bronchodilatator FEV1 >=30% and <=70% predicted normal value and FEV1/FVC ratio <0.7
• Documented history of at least 1 moderate or severe exacerbation in the 12 months prior to study entry
• Symptomatic patients (MMRC score ≥2 and a CAT score ≥10)
• Patients on daily maintenance therapy with an ICS/LABA .

Exclusion Criteria:

• Diagnosis of asthma or other respiratory disorders
• Maintenance bronchodilators therapy only (eg LABA alone)
• Maintenance triple therapy.
• Occurrence of a moderate or severe COPD exacerbation within 6 weeks prior to study entry or during the run-in period.
• Patients requiring long term oxygen therapy.
• Concomitant or recent pulmonary rehabilitation programme
• Known respiratory disorders other than COPD
• Lung cancer or a history of lung cancer, active or history of cancer with less than 5 years disease free survival time
• Hypersensitivity to β2-agonist, corticosteroids, PDE4 inhibitors or any of the excipients
• Depression, generalised anxiety disorder, suicidal ideation
• Any clinically significant cardiovascular disease (IM, CHF III/IV; AF not controlled by therapy, etc) within 1 year of study entry
• Any relevant clinically significant cardiovascular condition, clinically abnormal significant 12-lead ECG (QTcF>450 ms for male and >470 for female) or clinically significant laboratory abnormalities
• Serum potassium value ≤3.5 mEq/L or >5.5mEq/L and/or a fasting serum glucose value ≥140 mg/dL.
• History or symptoms of significant neurological disease
• Unstable concurrent disease: eg uncontrolled Thyroid disease or other endocrine diseases, gastrointestinal uncontrolled disease, uncontrolled immune diseases
• Renal impairment.
• Patients with abnormal alanine aminotransferase and/ or aspartate aminotransferase and/or bilirubin
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities and patients receiving treatment with any drug known to have a well defined potential for hepatotoxicity before Study entry
• Severely obese (BMI ≥35 kg/m2) or have experienced excessive weight loss recently
• History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit.
• Any recent participation to a clinical Study with other investigational drug