Evaluation of Tolerability and Pharmacokinetics of Roflumilast, 250μg and 500μg, as add-on to Standard COPD Treatment to Treat Severe COPD

Exclusion Criteria

• •Criteria affecting the read-out parameters of the study
• •1. Has a COPD exacerbation ongoing at the Screening (Visit V0), or has a COPD exacerbation between V0 and V1.
• •2. Has a lower respiratory tract infection not resolved 4 weeks prior to Screening (Visit V0).
• •3. Has a diagnosis of asthma and/or other relevant lung disease (eg, history of primary bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease \[eg, fibrosis, silicosis, sarcoidosis\], or active tuberculosis).
• •4. Has a known α1-antitrypsin deficiency.
• •5. Has taken roflumilast within 6 months of Screening (Visit V0).
• •Criteria within ethical considerations in terms of general health
• •6. Has clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the investigator).
• •7. Has a history of severe psychiatric or neurological disorders.
• •8. Has a history of depression associated with suicidal ideation or behavior.
• •9. Has congestive heart failure severity grade IV according to New York Heart Association (NYHA) Functional Classification.
• •10. Has hemodynamically significant cardiac arrhythmias or heart valve deformations.
• •11. Has computed tomography (CT) or chest x-ray findings indicating an acute pulmonary disease other than COPD (eg, tuberculosis, severe bronchiectasis, tumors).
• •12. Has severe immunological diseases (eg, known human immune deficiency virus (HIV) infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy).
• •13. Has liver impairment Child-Pugh B or C and/or active viral hepatitis.
• •14. Has severe acute infectious diseases (eg, tuberculosis, or acute hepatitis).
• •15. Has a history of malignant disease (except basal cell carcinoma) within 5 years before Screening (Visit V0).
• •16. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within one year before Screening (Visit V0).
• •17. Has a history of hypersensitivity or allergies to roflumilast or rescue medication or ingredients thereof, or any other contraindication for the use thereof.
• •18. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period.
• •19. Intends to donate blood, organs, or bone marrow during the course of the study.
• •20. Has received any investigational compound within 30 days prior to Screening (Visit V0), is currently participating in another interventional clinical study, or has been previously enrolled in this study.
• •21. Is suspected to be unable or unwilling to comply with study procedures (eg, language problems, psychological disorders, number and timing of visits at the center).
• •22. Suffers from any concomitant disease that might interfere with study procedures or evaluations.
• •23. Is required to take excluded medications.
• •24. Is an immediate family member, study center employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling), or may consent under duress.