Phase 1 Study Evaluating PALI-2108 in Healthy Volunteers and Ulcerative Colitis Patients.

Launched by PALISADE BIO · Oct 26, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new oral medication called PALI-2108, which is designed to help treat ulcerative colitis (UC), a condition that causes inflammation in the intestines. PALI-2108 works by targeting the intestines directly, which may reduce the risk of side effects compared to other medications. The trial will first test the safety and how the body processes the drug in healthy volunteers before including a small group of UC patients. Participants will take the medication either as a single dose or twice daily for seven days, and the researchers will monitor their health closely to see how well the drug works and if there are any side effects.

To be eligible for this trial, participants must be between 18 and 60 years old, have a specific diagnosis of moderate to severe ulcerative colitis, and be stable on standard treatments for at least three months. The study is open to both men and women, but there are specific health criteria that must be met to ensure everyone's safety. Overall, this trial aims to gather important information about PALI-2108, which could lead to new treatment options for people living with ulcerative colitis.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Inclusion criteria for all subjects and patients:
• • 1. Provision of signed and dated informed consent form (ICF)
• • 2. Stated willingness to comply with all study procedures and availability for the duration of the study
• 3. If male, meets one of the following criteria:
• 1. Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last study drug administration. An acceptable method of contraception includes one of the following:
• • Abstinence from heterosexual intercourse
• • Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository) Or
• • 2. Is unable to procreate; defined as surgically sterile (eg, has undergone a vasectomy at least 180 days prior to the first study drug administration)
• 4. If female, is of non-childbearing potential and meets one of the following criteria:
• • 1. Is surgically sterile (ie, has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) Or
• 2. Is in a postmenopausal state:
• • At least 1 year without menses and without an alternative medical condition prior to the Screening visit and follicle stimulating hormone \[FSH\] levels ≥ 40 mIU/mL at Screening Or
• • At least 1 year without menses and without an alternative medical condition prior to the Screening visit, follicle stimulating hormone FSH levels \< 40 mIU/mL and estradiol serum level ≤ 150 pmol/L at Screening
• • 5. Aged at least 18 years but not older than 60 years
• • 6. Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
• • 7. Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration)
• Inclusion criteria for SAD, MAD, and FE parts (healthy subjects):
• • 8. Healthy adult male or female
• • 9. Have no clinically significant (CS) diseases captured in the medical history or evidence of CS findings on the physical examination (including vital signs) and/or ECG, as determined by an Investigator
• Inclusion criteria for UC patients:
• • 10. Adult male or female
• • 11. Diagnosis of moderate to severe UC, established at least 6 months prior to Screening; Mayo Score ≥ 6 with rectal bleeding score (RBS) ≥ 1, stool frequency score (SFS) ≥ 1, (mucosal endoscopic score (MES) ≥ 2, and with disease extending ≥ 15 cm from anal verge, and physician's global assessment (PGA)
• • 12. Stable UC symptoms and severity for at least 3 months prior to Screening
• • 13. Well controlled with standard of care therapy for IBD including on stable treatment with aminosalicylates, immunomodulators (eg, methotrexate, azathioprine), or steroids (≤ 20 mg prednisone or equivalent); use of standard of care UC therapies must be stable for at least 4 weeks prior to Screening
• Exclusion Criteria:
• Exclusion criteria for all subjects and patients:
• • 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 PDE4 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 in the 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
• Exclusion criteria for SAD, MAD, and FE parts (healthy subjects):
• • 23. Use of any prescription drugs in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy
• • 24. Subjects with less than 3 bowel movements or more than 3 episodes of diarrhea (loose watery stools) per week within the month prior to Screening
• • 25. Subjects with history of irritable bowel syndrome and functional dyspepsia
• Exclusion criteria for UC patients:
• • 26. Greater than 2 prior biologic failures
• • 27. Use of a biologic medication within 3 months prior to Screening
• • 28. Use of PDE-4 inhibitors within 3 months prior to Screening
• • 29. History of bariatric surgery, total colectomy with ileorectal anastomosis, or proctocolectomy
• • 30. Presence of a postoperative stoma, ostomy, or ileoanal pouch
• • 31. Participants with any uncontrolled medical conditions, other than active UC, that in the opinion of the Investigator, would put the participant at unacceptable risk or interfere with study assessments or integrity of the data. Other medical conditions should be stable at the time of Screening and be expected to remain stable for the duration of the study
• • 32. Current or history of chronic liver or biliary disease (with the exception of Gilbert's syndrome, asymptomatic gallstones, or uncomplicated fatty liver disease)