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

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