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

NCT06663605 | Completed Phase 1 DMC

• 1 other identifier: PBI-2108-101
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

PALI-2108 is a new oral medication designed to treat ulcerative colitis (UC) by targeting the intestines. It works as a phosphodiesterase-4 (PDE4) inhibitor prodrug, meaning it becomes active only after being processed by bacteria in the colon. This targeted approach reduces the risk of side effects that can occur with other medications that affect the entire body. Recent studies have shown that patients with active UC, especially those with moderate to severe symptoms, have higher levels of PDE4 and related biomarkers. These biomarkers are linked to the severity of their disease, suggesting that inhibiting PDE4 could help manage UC effectively. The goal of this Phase 1 study is to evaluate the safety, tolerability, and how the body processes (pharmacokinetics) and responds to (pharmacodynamics) PALI-2108 in healthy volunteers. Although there are already PDE4 inhibitors on the market, PALI-2108 is a completely new compound that has not been tested in humans before. The study will involve two parts: first, participants will receive single doses of the drug, and then, in the second part, they will take it twice a day for seven days. The twice-daily dosing schedule is designed to maximize drug exposure in the colon. The investigators will also investigate how food affects the drug's absorption. Additionally, a small group of stable UC patients will be included in the study. These patients will also take PALI-2108 for seven days, allowing us to compare the safety and drug processing between healthy individuals and those with UC. The investigators will monitor important health markers and conduct tests on colon tissue to see how well the drug works and if it causes any changes in the tissue. Including UC patients early in this research is important for understanding how the drug performs in real-world conditions. This data will help refine our approach to identify which patients might benefit most from PALI-2108 in future studies. Overall, this study aims to gather crucial information about PALI-2108's safety and effectiveness, paving the way for new treatment options for patients with ulcerative colitis.

Conditions

Ulcerative Colitis (UC); Healthy Volunteer

Keywords

Phase 1 for PALI-2108 in Healthy Volunteers and UC patients; Ulcerative colitis; PALI-2108

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (TEAE) or abnormal clinical laboratory measure, electrocardiogram (ECG), or vital sign. [ Safety and Tolerability ]

  Incidence of Treatment Emergent Adverse Events (TEAE) or abnormal clinical laboratory measure, electrocardiogram (ECG), or vital sign.

  SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 28 ]

Secondary Outcomes (19)

• Maximum (or peak) plasma concentration (Cmax)

  SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]

• Area Under the Curve from dosing to the time of the last measured concentration (AUC0-T)

  SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]

• Area under the curve from time 0 extrapolated to infinite time (AUCinf)

  SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]

• Time to reach Cmax (Tmax)

  SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]

• Terminal half-life (t1/2)

  SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]

Other Outcomes (10)

• Phosphodiesterase-4 (PDE4)-related pharmacodynamic (PD) biomarkers in MAD and UC

  MAD and UC Cohort: [ Day 1 to Day 7 ]

• Cyclic adenosine monophosphate (cAMP) in MAD and UC

  MAD and UC Cohort: [ Day 1 to Day 7 ]

• Colonic tissue drug concentration (Ctissue) in MAD and UC

  MAD and UC Cohort: [ Day 1 to Day 7 ]

Study Arms (2)

PALI-2108

EXPERIMENTAL

Part A - Single Ascending oral doses of PALI-2108 in healthy adult subjects. Part B - Single oral dose crossover of PALI-2108 in healthy adult subjects. Part C - Multiple Ascending oral Doses of PALI-2108 in healthy adult subjects. Part D - (open-label) Multiple oral Doses of PALI-2108 in Ulcerative Colitis patients.

Drug: PALI-2108

PALI-2108 Placebo

PLACEBO COMPARATOR

Part A - Single Ascending oral Dose of matching placebo in healthy adult subjects. Part B - Single Ascending oral Dose of matching placebo crossover of PALI-2108 in healthy adult subjects. Part C - Multiple Ascending oral Doses of matching placebo in healthy adult subjects. Part D - (open-label) Multiple Ascending oral Doses of matching placebo in Ulcerative Colitis patients.

Drug: PALI-2108 Placebo

Interventions

PALI-2108 DRUG

Oral dose

Also known as: PALI-2108 active drug

PALI-2108

PALI-2108 Placebo DRUG

Oral dose

PALI-2108 Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form (ICF)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• If male, meets one of the following criteria:
• 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
• Is unable to procreate; defined as surgically sterile (eg, has undergone a vasectomy at least 180 days prior to the first study drug administration)
• If female, is of non-childbearing potential and meets one of the following criteria:
• Is surgically sterile (ie, has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) Or
• 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
• Aged at least 18 years but not older than 60 years
• Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
• 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)

You may not qualify if:

• Female who is lactating
• Female who is pregnant according to the pregnancy test at Screening or Day -1
• 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
• Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability or transit
• Presence of history of renal disease
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
• An active infection or a recent history of serious infections in the 30 days prior to first study drug administration
• 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
• Major surgery in the 4 weeks prior to the first study drug administration
• Vaccination with any live vaccine within 4 weeks prior to study drug administration
• 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)
• Any CS illness in the 28 days prior to the first study drug administration
• Use of St. John's wort in the 28 days prior to the first study drug administration
• Any history of tuberculosis
• Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration

Sponsors & Collaborators

• Palisade Bio: lead
• Altasciences Company Inc.: collaborator

Study Sites (1)

Altasciences

Montreal, Quebec, H3P3H5, Canada

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Mitchell L Jones, MD, PhD

  Palisade Bio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 a/b Double-Blind, Placebo-Controlled, Randomized Single Ascending Dose (SAD)/Multiple Ascending Dose (MAD), Food Effects (FE) crossover and Open-Label Ulcerative Colitis patient cohort study

Study Record Dates

• First Submitted: October 25, 2024
• First Posted: October 29, 2024
• Study Start: November 5, 2024
• Primary Completion: July 7, 2025
• Study Completion: August 7, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

CA (1)