Ulcerative Colitis (UC)Phase 1NCT06663605
Phase 1 Study Evaluating PALI-2108 in Healthy Volunteers and Ulcerative Colitis Patients.
A Phase 1 study testing PALI-2108 in people with Ulcerative Colitis (UC) and Healthy Volunteer, run by Palisade Bio at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Ulcerative Colitis (UC), Healthy Volunteer
- What is being tested?
- PALI-2108
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 89 participants
- Where
- 1 siteCanada
- Study dates
- 5 Nov 2024to 7 Aug 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 22Show fewer
- 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)
- Inclusion criteria for SAD, MAD, and FE parts (healthy subjects):
- Healthy adult male or female
- 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
- Adult male or female
- 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)
- Stable UC symptoms and severity for at least 3 months prior to Screening
- 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
Who cannot join
- 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
Show all 33Show fewer
- 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
- Positive Screening results to HIV antigen/antibody (Ag/Ab) combo, hepatitis B surface antigen, or hepatitis C virus tests
- 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
- Inclusion in a previous group for this clinical study
- Intake of PALI-2108 in the 28 days prior to the first study drug administration
- Intake of an investigational drug in the 28 days prior to the first study drug administration
- Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
- 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):
- 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
- 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
- Subjects with history of irritable bowel syndrome and functional dyspepsia
- Greater than 2 prior biologic failures
- Use of a biologic medication within 3 months prior to Screening
- Use of PDE-4 inhibitors within 3 months prior to Screening
- History of bariatric surgery, total colectomy with ileorectal anastomosis, or proctocolectomy
- Presence of a postoperative stoma, ostomy, or ileoanal pouch
- 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
- Current or history of chronic liver or biliary disease (with the exception of Gilbert's syndrome, asymptomatic gallstones, or uncomplicated fatty liver disease)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Double-Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of PALI-2108 in Healthy Volunteers and Open-Label Study of a Patient Cohort With Ulcerative Colitis
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.
Read more
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.
Read the detailed description
PALI-2108 is a novel synthetic prodrug designed to function as an intestinally activated phosphodiesterase-4 (PDE4) inhibitor, with a unique galactose sugar moiety linked by a beta 1,4 bond that enhances its targeted delivery within the colon. This innovative formulation minimizes systemic exposure and potential central nervous system (CNS) mediated toxicity by being cleaved by colonic bacterial enzyme β-glucuronidase, thus releasing the active PDE4 inhibitor directly in the colonic tissue. This mechanism is particularly advantageous in treating conditions like ulcerative colitis (UC), where localized treatment can enhance safety and efficacy.
Recent proprietary bioinformatics analyses indicate that patients with active UC, especially those with moderate to severe disease, exhibit significantly elevated levels of PDE-4 and PDE-4 related transcriptional biomarkers. These biomarkers have been found to correlate with established markers of UC disease activity and severity, such as the Mayo score. This highlights the potential role of PDE-4 inhibition in managing UC, making PALI-2108 a promising candidate for further investigation.
The primary aim of this single-center Phase 1 study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PALI-2108 in healthy volunteers. Although several PDE-4 inhibitors have received market approval, but not in Ulcerative Colitis, PALI-2108 represents a new chemical entity that has not been previously administered to humans. The study will consist of single ascending dose (SAD) cohorts followed by multiple ascending dose (MAD) cohorts, with participants receiving twice-daily (BID) dosing for seven consecutive days. This BID regimen is designed to optimize colonic exposure to the active PDE4 inhibitor.
In addition to healthy volunteers, a small cohort of stable moderate to severe UC patients will be included in the study. These patients, who will be under standard care, will also receive BID dosing for seven days. Comprehensive safety monitoring and similar PK evaluations will be conducted in this cohort. Biomarkers, including high sensitivity C-reactive protein (hsCRP) and fecal calprotectin (CalPro), along with colonic tissue histological assessments, will be employed to provide further insights into the drug's effects. The analysis of colon tissue will include the study drug and metabolite levels, PDE4 expression, and related PD biomarkers, which are crucial for understanding the drug's mechanism and efficacy.
This early inclusion of UC patients is strategic, allowing for the correlation of PK/PD profiles between healthy volunteers and UC subjects. It also enables close monitoring of safety within a controlled clinical pharmacology unit. The comprehensive data gathered will support Palisade Bio's Precision Medicine Strategy, aimed at identifying patient responders for future clinical studies. Overall, the study of PALI-2108 has the potential to advance therapeutic options for UC, emphasizing localized treatment and improved patient safety.
- Conditions
- Ulcerative Colitis (UC), Healthy Volunteer
- Being tested
- PALI-2108, PALI-2108 Placebo
- Keywords
- Phase 1 for PALI-2108 in Healthy Volunteers and UC patients, Ulcerative colitis, PALI-2108
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PALI-2108Drug
Also called PALI-2108 active drug
Oral dose
PALI-2108 PlaceboDrug
Oral dose
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: PALI-2108 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
PK parameters calculated for plasma PALI-2108, PALI-0008, and PALI-0708.
Measured: 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)
PK parameters calculated for plasma PALI-2108, PALI-0008, and PALI-0708.
Measured: 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)
PK parameters calculated for plasma PALI-2108, PALI-0008, and PALI-0708.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Time to reach Cmax (Tmax)
PK parameters calculated for plasma PALI 2108, PALI 0008, and PALI-0708.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Terminal half-life (t1/2)
PK parameters calculated for plasma PALI 2108, PALI 0008, and PALI-0708.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Ratio of oral clearance (CL/F) (parent only)
PK parameters calculated for plasma PALI 2108.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Volume of distribution (Vd/F) (parent only)
PK parameters calculated for plasma PALI 2108.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Ratio of unchanged drug to metabolite (Metabolic ratio) (Cmax)
PK parameters calculated for plasma Cmax.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Ratio of unchanged drug to metabolite (Metabolic ratio) (AUC)
PK parameters calculated for plasma AUC.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Concentration of drug and metabolites in feces (C24,f)
Concentration of PALI-2108, PALI-0708, and PALI-0008 in feces.
Measured: MAD and UC Cohort: [ Day 1 to Day 10 ]
Fecal/colonic mucosa drug concentration ratio at steady state (SS).
Fecal/colonic mucosa drug concentration ratios of PALI-2108, PALI-0708, and PALI-0008 at Steady State (SS).
Measured: 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 (AUC0-12)
PK parameters calculated in plasma for PALI-2108, PALI-0008, and PALI-0708.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Cumulative drug excreted unchanged in urine (Aetau)
Cumulative drug excreted unchanged into urine during a dosing interval (Aetau)
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Cumulative drug excreted unchanged in urine over 24h (Ae0-24)
Cumulative drug excreted unchanged in urine over 24h (Ae0-24)
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Fraction of drug dose excreted unchanged into urine (fe)
Fraction of dose excreted unchanged into urine as a percentage (%)
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Renal clearance of drug (CLr) (parent only)
Renal clearance of drug (CLr) of parent only.
Measured: 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 (AUC0-12)
PK parameters calculated for plasma PALI-2108, PALI-0008, and PALI-0708.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Time to last plasma concentration (Tlast)
PK parameters calculated for plasma PALI-2108, PALI-0008, and PALI-0708.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Terminal rate constant (λz)
PK parameters calculated for plasma PALI 2108, PALI 0008, and PALI-0708.
Measured: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2024
- Study start5 Nov 2024
- Primary completion7 Jul 2025
- Study completion7 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative Colitis (UC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Palisade Bio
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Altasciences Company Inc.
- Responsible party
- Sponsor
- Investigators
- Mitchell L Jones, MD, PhD, Principal investigator, Palisade Bio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06663605
- Sponsor's protocol ID
- PBI-2108-101
- Status last verified
- Aug 2025
- First submitted
- 25 Oct 2024
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Double-Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of PALI-2108 in Healthy Volunteers and Open-Label Study of a Patient Cohort With Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT06663605
- Acronym / sponsor ID
- PBI-2108-101
- Conditions
- Ulcerative Colitis (UC), Healthy Volunteer
- Keywords
- Phase 1 for PALI-2108 in Healthy Volunteers and UC patients, Ulcerative colitis, PALI-2108
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Palisade BioIndustry (pharma, biotech, devices)
- Collaborators
- Altasciences Company Inc.
- Study start
- 5 Nov 2024 (actual)
- Primary completion
- 7 Jul 2025 (actual)
- Study completion
- 7 Aug 2025 (actual)
- First posted
- 29 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PALI-2108 is a novel synthetic prodrug designed to function as an intestinally activated phosphodiesterase-4 (PDE4) inhibitor, with a unique galactose sugar moiety linked by a beta 1,4 bond that enhances its targeted delivery within the colon. This innovative formulation minimizes systemic exposure and potential central nervous system (CNS) mediated toxicity by being cleaved by colonic bacterial enzyme β-glucuronidase, thus releasing the active PDE4 inhibitor directly in the colonic tissue. This mechanism is particularly advantageous in treating conditions like ulcerative colitis (UC), where localized treatment can enhance safety and efficacy.
Recent proprietary bioinformatics analyses indicate that patients with active UC, especially those with moderate to severe disease, exhibit significantly elevated levels of PDE-4 and PDE-4 related transcriptional biomarkers. These biomarkers have been found to correlate with established markers of UC disease activity and severity, such as the Mayo score. This highlights the potential role of PDE-4 inhibition in managing UC, making PALI-2108 a promising candidate for further investigation.
The primary aim of this single-center Phase 1 study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PALI-2108 in healthy volunteers. Although several PDE-4 inhibitors have received market approval, but not in Ulcerative Colitis, PALI-2108 represents a new chemical entity that has not been previously administered to humans. The study will consist of single ascending dose (SAD) cohorts followed by multiple ascending dose (MAD) cohorts, with participants receiving twice-daily (BID) dosing for seven consecutive days. This BID regimen is designed to optimize colonic exposure to the active PDE4 inhibitor.
In addition to healthy volunteers, a small cohort of stable moderate to severe UC patients will be included in the study. These patients, who will be under standard care, will also receive BID dosing for seven days. Comprehensive safety monitoring and similar PK evaluations will be conducted in this cohort. Biomarkers, including high sensitivity C-reactive protein (hsCRP) and fecal calprotectin (CalPro), along with colonic tissue histological assessments, will be employed to provide further insights into the drug's effects. The analysis of colon tissue will include the study drug and metabolite levels, PDE4 expression, and related PD biomarkers, which are crucial for understanding the drug's mechanism and efficacy.
This early inclusion of UC patients is strategic, allowing for the correlation of PK/PD profiles between healthy volunteers and UC subjects. It also enables close monitoring of safety within a controlled clinical pharmacology unit. The comprehensive data gathered will support Palisade Bio's Precision Medicine Strategy, aimed at identifying patient responders for future clinical studies. Overall, the study of PALI-2108 has the potential to advance therapeutic options for UC, emphasizing localized treatment and improved patient safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| PALI-2108 | Experimental | Drug: PALI-2108Part 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. |
| PALI-2108 Placebo | Placebo comparator | Drug: PALI-2108 PlaceboPart 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- 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:
- If female, is of non-childbearing potential and meets one of the following criteria:
- Aged at least 18 years but not older than 60 years
Key exclusion criteria (33 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PALI-2108Also: PALI-2108 active drugOral dose | Drug | PALI-2108 |
| PALI-2108 PlaceboOral dose | Drug | PALI-2108 Placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (TEAE) or abnormal clinical laboratory measure, electrocardiogram (ECG), or vital sign. [ Safety and Tolerability ]
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 28 ]
Incidence of Treatment Emergent Adverse Events (TEAE) or abnormal clinical laboratory measure, electrocardiogram (ECG), or vital sign.
19 secondary outcomes
Maximum (or peak) plasma concentration (Cmax)
Time frame: 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)
Time frame: 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)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Time to reach Cmax (Tmax)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Terminal half-life (t1/2)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Ratio of oral clearance (CL/F) (parent only)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Volume of distribution (Vd/F) (parent only)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Ratio of unchanged drug to metabolite (Metabolic ratio) (Cmax)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Ratio of unchanged drug to metabolite (Metabolic ratio) (AUC)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Concentration of drug and metabolites in feces (C24,f)
Time frame: MAD and UC Cohort: [ Day 1 to Day 10 ]
Fecal/colonic mucosa drug concentration ratio at steady state (SS).
Time frame: 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 (AUC0-12)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Cumulative drug excreted unchanged in urine (Aetau)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Cumulative drug excreted unchanged in urine over 24h (Ae0-24)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Fraction of drug dose excreted unchanged into urine (fe)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Renal clearance of drug (CLr) (parent only)
Time frame: 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 (AUC0-12)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Time to last plasma concentration (Tlast)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Terminal rate constant (λz)
Time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 10 ]
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitchell L Jones, MD, PhD principal investigator
Palisade Bio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PALI-2108 in people with Ulcerative Colitis (UC) and Healthy Volunteer, run by Palisade Bio at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (TEAE) or abnormal clinical laboratory measure, electrocardiogram (ECG), or vital sign. [ Safety and Tolerability ] (time frame: SAD and FE Phase: [ Day 1 to Day 7 ], MAD and UC Phase: [ Days 1 to Day 28 ]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.