Roflumilast Plus Alogliptin Proof-of-Mechanism Study in Type2 Diabetes

Exclusion Criteria

• •1. Has a history of type 1 diabetes.
• •2. Has a history of acute metabolic diabetic complications.
• •3. Has has abnormal Screening or Check-in (Day -2) laboratory values that suggest a clinically significant underlying disease (eg, active liver disease or jaundice) or participant with the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>3 × upper limit of normal (ULN).
• •4. Has a history of diabetic gastroparesis or history of gastric bypass surgery.
• •5. Has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
• •6. Has New York Heart Association heart failure of Class (III-IV) regardless of therapy.
• •7. Has a supine blood pressure \>150 mm Hg for systolic or \>90 mm Hg for diastolic, confirmed on repeat testing within a maximum of 5 minutes, at Screening and Check-in (Day -2).
• •8. Has presence or history of neuropsychiatric disorder (eg, psychosis, psychotic disorders, depression associated with suicidal thinking, suicidal ideation or behavior).
• •9. 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 4 alcoholic drinks per day) within the past 2 years or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• •10. Has a hemoglobin ≤120 g/L for men and ≤100 g/L for women.
• •11. Has a history of clinically significant allergies or idiosyncrasies to roflumilast, alogliptin and exenatide or any inactive ingredient(s) of these products, eg, rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or phenylketonuria.
• •12. Has received alogliptin or roflumilast in a previous clinical study or as a therapeutic agent within 2 months prior to Screening, or is taking prescription roflumilast for chronic obstructive pulmonary disease (COPD), or has received any other investigational compound within 30 days prior to the first dose of study medication, or is participating or plans to participate in any other clinical trial during this study.
• •13. If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after last dose; or intending to donate ova during such time period.
• •14. If male, intends to donate sperm during the course of the study or for 30 days after last dose of study medication.
• •15. Is an immediate family member, study site employee, or in a dependent 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.
• •16. Has a history of cancer, except basal cell or squamous cell carcinoma which has been in remission for at least 5 years prior to Day 1.
• •17. Serum creatinine ≥1.5 mg/dL for males and ≥1.4 mg/dL for females or creatinine clearance \<60 mL/minutes, based on calculation by central lab using the Cockcroft-Gault approximation at Screening Visit.
• •18. Has a history of any hemoglobinopathy that may affect determination of HbA1c.
• •19. Has positive test result for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV), any known history of infection with human immunodeficiency virus (HIV), any acute infection, or severe immunological diseases (eg, multiple sclerosis, systemic lupus erythematosus, and progressive multifocal leukoencephalopathy).
• •20. Has a risk of suicide according to the Investigator's clinical judgment per Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or has made a suicide attempt in the past 6 months.
• •21. Has any clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (as assessed by the investigator).
• •22. Does not have an adequate standard of literacy to allow him or her to complete the study diary during non-clinic days.
• •23. Has poor peripheral venous access.
• •24. Has Screening or Check-in (Day -2) abnormal clinically significant electrocardiogram (ECG). Entry of any participant with abnormal not clinically significant ECG must be approved and documented by signature of Principal Investigator and Medical Monitor.