A Study of PALI-2108 in Healthy Volunteers, Patients With Ulcerative Colitis, and Patients With Fibrostenosing Crohn's Disease

Exclusion Criteria

• •1. Female who is lactating
• •2. Female who is pregnant according to the pregnancy test at Screening or Day -1
• •3. History of significant hypersensitivity to PALI-2108 or any other PDE-4 inhibitor (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• •4. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability or transit
• •5. Presence of history of renal disease
• •6. History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
• •7. An active infection or a recent history of serious infections 30 days prior to first study drug administration
• •8. Presence of CS vital sign and/or ECG abnormalities (based on the average of triplicate ECG readings) at the Screening visit, as defined by medical judgment
• •9. Major surgery in the 4 weeks prior to the first study drug administration
• •10. Vaccination with any live vaccine within 4 weeks prior to study drug administration
• •11. Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• •12. Any CS illness in the 28 days prior to the first study drug administration
• •13. Use of St. John's wort in the 28 days prior to the first study drug administration
• •14. Any history of tuberculosis
• •15. Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration
• •16. Positive Screening results to HIV antigen/antibody (Ag/Ab) combo, hepatitis B surface antigen, or hepatitis C virus tests
• •17. Any other CS abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
• •18. Inclusion in a previous group for this clinical study
• •19. Intake of PALI-2108 in the 28 days prior to the first study drug administration
• •20. Intake of an investigational drug in the 28 days prior to the first study drug administration
• •21. Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
• •22. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration
• •23. History or current diagnosis of UC, indeterminate colitis, ischemic colitis, nonsteroidal anti-inflammatory drug-induced colitis, idiopathic colitis (ie, colitis not consistent with CD), radiation colitis, microscopic colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
• •24. CD related complications (previous extensive small bowel resection, ileorectal anastomosis, proctocolectomy, short bowel syndrome, ileostomy \[diverting or end\], colostomy, small bowel stoma, ileoanal pouch, inactive fistulae in or adjacent to an ileal stricture, anal and perianal stricture, active intra-abdominal or perianal abscess that has not been appropriately treated, abscess in relation to the stricture, toxic megacolon, very severe inflammation, or presence of deep ulceration in the colon or terminal ileum).
• •25. Ileitis not associated with CD (e.g., ileitis associated with infections, spondyloarthropathies, ischemia, etc.).
• •26. Strictures that cannot be reached by ileocolonoscopy
• •27. Severe FSCD based on symptoms, or unstable disease
• •28. Expected to require hospitalization, endoscopic balloon dilation, surgical resection, or additional therapy during the study
• •29. Receiving cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks of screening or Janus kinase inhibitor therapy within 4 weeks of screening.
• •30. Current or history of vasculitis, valvulopathy or large vessel disorder or major abnormalities documented by cardiac echocardiography with Doppler