Roflumilast plus Montelukast in Adults with Severe Asthma

Exclusion Criteria

• 1. Has received any investigational compound within 30 days prior to the start of the clinical trial or has participated in the active treatment phase of another clinical trial where a persisting pharmacodynamic effect of the trial treatment of that clinical trial cannot be excluded (eg, participant is well into a treatment free follow-up phase).
• 2. Participation in another clinical trial during the current trial.
• 3. Is an immediate family member, study site 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.
• 4. Severe asthma exacerbation not resolved 4 weeks prior to Visit 1, (defined by the need for oral or parenteral glucocorticosteroid intake for at least 3 days and/or hospitalization or emergency room visit with the need for oral or parenteral corticosteroid use).
• 5. Lower respiratory tract infection not resolved 4 weeks prior to Visit 1.
• 6. A diagnosis of chronic obstructive pulmonary disease (COPD) (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] criteria) and/or other relevant forms of lung disease (eg, history of primary bronchiectasis, cystic fibrosis, idiopathic (pan)bronchiolitis or bronchiolitis obliterans, bronchopulmonary allergic aspergillosis, Churg-Strauss Syndrome, paradoxical vocal cord closure, lung resection, lung cancer, interstitial lung disease [eg, fibrosis, silicosis, sarcoidosis], or active tuberculosis) that may interfere with the evaluation of a treatment response.
• 7. Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding Visit 1.
• 8. Has, in the judgment of the investigator, clinically significant abnormal laboratory values (hematology or biochemistry) at screening suggesting an undiagnosed disease requiring further clinical evaluation.
• 9. Has severe neuropsychiatric or neurological disorders (eg, history of depression associated with suicidal thinking, suicidal ideation or behavior).
• 10. Has congestive heart failure severity grade III or IV according to the New York Heart Association.
• 11. Has symptomatic ischemic heart disease (angina pectoris).
• 12. Has hemodynamically significant cardiac arrhythmias or heart valve deformations.
• 13. Has liver impairment, defined as Child-Pugh B/C and/or active viral hepatitis.
• 14. Has severe immunological diseases (eg, multiple sclerosis, systemic lupus erythematosus, progressive multifocal leukoencephalopathy) or known infection with human immunodeficiency virus (HIV).
• 15. Has severe acute infectious diseases (eg, tuberculosis, or acute hepatitis).
• 16. Has any diagnosis of a malignant disease (other than basal or squamous cell carcinoma) within 5 years prior to Screening Visit 1.
• 17. Has a history of smoking within 1 year of Visit 1 and smoking history ≥10 pack years.
• 18. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within the past 1 year prior to the Screening visit.
• 19. Has history of clinically significant allergies or idiosyncrasies to roflumilast, montelukast or any inactive ingredient(s) of these products, eg, rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or phenylketonuria.
• 20. Has known highly unstable asthma defined by severe bronchoconstriction after bronchoprovocation with isotonic saline.
• 21. Females of childbearing potential not willing to use acceptable contraceptive methods such as hormonal contraceptives (oral, injection or implant) or intrauterine contraceptive devices or who started such methods less than 2 months prior to screening or who are not willing to use a double barrier method of contraception (diaphragm plus condom).
• 22. If female, is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
• 23. Is required to take excluded medication.