Roflumilast Plus Antipsychotics Proof of Mechanism Study in Schizophrenia

Exclusion Criteria

• •1. Has received any investigational compound within 30 days prior to the first dose of study medication.
• •2. Has received roflumilast in a previous clinical study or as a therapeutic agent.
• •3. Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• •4. Has uncontrolled, clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
• •5. History of claustrophobia or inability to tolerate mock scanner environment during habituation/screening session.
• •6. Fulfillment of any of the magnetic resonance imaging (MRI) contraindications on the standard radiography screening questionnaire at the Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London (ie, history of surgery involving metal implants, metal body piercing, dentures, dental plates or bridges, any implanted device that is electrically, magnetically, and mechanically activated).
• •7. Has a known hypersensitivity to any component of the formulation of roflumilast.
• •8. Has a positive urine drug result for drugs of abuse at Screening or Day 1 for each treatment period.
• •9. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 6 months prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• •10. The participant with a history in the last year or currently receiving treatment with clozapine.
• •11. Has taken any excluded medication, supplements, or food products.
• •12. If female, the participant 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.
• •13. Has evidence of current cardiovascular, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking roflumilast or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
• •14. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, or erosive esophagitis frequent occurrence \[more than once per week\] of heartburn).
• •15. History of any surgical intervention known to impact absorption (eg, bariatric surgery or bowel resection).
• •16. Has a history of cancer within the past 5 years prior to the first dose of study medication. This criterion does not include those participants with basal cell or stage I squamous cell carcinoma of the skin who are eligible.
• •17. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen at Screening.
• •18. Has poor peripheral venous access.
• •19. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1.
• •20. Has a Screening or Day 1 of Period 1 abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator.
• •21. Has abnormal Screening or Day 1 of Period 1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 the upper limits of normal.
• •22. Has abnormal Screening or Day 1 of Period 1 vital sign values that suggest a clinically significant underlying disease.
• •23. Has a risk of suicide according to the Investigator's clinical judgment (eg, per Columbia-Suicide Severity Rating Scale \[C-SSRS\] or has made a suicide attempt within 6 months prior to screening visit).
• •24. Has a current diagnosis of a significant psychiatric illness other than schizophrenia, per DSM-V and is in an acute phase/episode.
• •25. In the opinion of the investigator or sponsor, the participant is unsuitable for inclusion in the study.