PALI-2108 for Ulcerative Colitis

Overseen By Patrick Colin, BPharm, MSc, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Palisade Bio

Must be taking: Aminosalicylates, Immunomodulators, Steroids

Must not be taking: Biologics, PDE-4 inhibitors

Disqualifiers: Pregnancy, Renal disease, Cardiovascular, others

Compensation: Varies

Number of Visits: 21

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, UC patients must be on stable treatment with aminosalicylates, immunomodulators, or steroids for at least 4 weeks before the study. If you are taking biologics or PDE-4 inhibitors, you must stop them 3 months before the study.

Is PALI-2108 safe for humans?

The studies available focus on palonosetron, which is similar to PALI-2108, and show it is generally safe for preventing nausea and vomiting in cancer patients undergoing chemotherapy. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Mitchell L Jones, MD, PhD

Principal Investigator

Palisade Bio

Eligibility Criteria

This trial is for healthy volunteers and stable ulcerative colitis (UC) patients. Participants should be adults who can take oral medication. The study excludes individuals with other significant health issues, those on certain medications that might interfere with the trial, or anyone unable to comply with study requirements.

Inclusion Criteria

Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2

I am a healthy adult with no significant health issues.

I have moderate to severe ulcerative colitis that is stable and well-controlled with current treatment.

Exclusion Criteria

History of significant hypersensitivity to PALI-2108 or any other PDE4 inhibitor

I have a history of kidney disease.

I do not have an active infection or a recent history of serious infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Healthy volunteers receive single ascending doses of PALI-2108 to evaluate safety and pharmacokinetics

1 week

Daily visits for 7 days

Multiple Ascending Dose (MAD)

Healthy volunteers receive multiple ascending doses of PALI-2108 twice daily for seven days to assess safety and pharmacokinetics

1 week

Daily visits for 7 days

Ulcerative Colitis Patient Cohort

Stable UC patients receive PALI-2108 twice daily for seven days to compare safety and pharmacokinetics with healthy volunteers

1 week

Daily visits for 7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PALI-2108

Trial Overview PALI-2108, a new oral drug targeting UC by becoming active in the colon, is being tested for safety and how it's processed by the body. Healthy participants will first receive single doses; then they'll take it twice daily for a week. A small group of UC patients will do the same to compare results.

Participant Groups

Group I: PALI-2108 Experimental Treatment 1 Intervention

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.

Group II: PALI-2108 Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Palisade Bio

Lead Sponsor

Trials

3

Recruited

230+

Altasciences Company Inc.

Industry Sponsor

Trials

18

Recruited

860+

Findings from Research

In a study of 134 patients with acute myeloid leukemia, the combination of palonosetron and aprepitant was found to significantly reduce nausea compared to palonosetron alone, with 43% of patients experiencing no nausea versus 27% in the single-drug group.

While the overall complete response rates for preventing vomiting were similar between the two treatments (72% vs 69%), the combination therapy also showed a longer time to anti-emetic treatment failure, indicating better overall control of chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia: A randomized, controlled study from the "Rete Ematologica Pugliese". Di Renzo, N., Melillo, L., Porretto, F., et al.[2021]

In a study of 34 cancer patients who previously experienced nausea and vomiting from low emetogenic chemotherapy, intravenous palonosetron effectively prevented chemotherapy-induced nausea and vomiting, achieving complete response rates of 88.2% in the acute phase and 67.6% in the delayed phase.

Palonosetron was well tolerated, with only two patients reporting treatment-related adverse events, indicating a favorable safety profile for this medication in managing CINV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palonosetron as salvage treatment in the prevention of chemotherapy-induced nausea and vomiting in patients receiving low emetogenic chemotherapy (LEC). Hesketh, PJ., Morrow, G., Komorowski, AW., et al.[2022]

In a study involving 60 pediatric patients in Japan, palonosetron was found to be effective in preventing chemotherapy-induced nausea and vomiting, achieving a complete response rate of 58.6%, which exceeded the primary endpoint threshold of 30%.

The treatment was well-tolerated, with only 3.4% of patients experiencing treatment-related adverse events, and the pharmacokinetics of palonosetron were consistent across different age groups, supporting the use of a 20 μg/kg dose for all pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study of palonosetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients. Hara, J., Kosaka, Y., Koh, K., et al.[2021]

Aprepitant, when used with standard anti-nausea medications, was well tolerated and effective in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with colorectal cancer receiving moderately emetogenic chemotherapy, based on a multicenter phase II study.

The study found no significant differences in complete response rates or secondary outcomes between the aprepitant group and the standard treatment group, indicating that aprepitant is a viable option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II, randomized study of aprepitant in the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients. Aridome, K., Mori, SI., Baba, K., et al.[2020]

In a study involving 68 chemotherapy-naive patients with breast cancer or colorectal cancer, the combination of palonosetron and dexamethasone resulted in a complete response (no vomiting and no need for rescue medication) in 67.6% of participants over a 5-day period.

The treatment was well tolerated and effectively controlled chemotherapy-induced nausea and vomiting (CINV) during both the acute and delayed phases, with a complete response rate of 75% in each cancer group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose palonosetron and dexamethasone in preventing nausea and vomiting induced by moderately emetogenic chemotherapy in breast and colorectal cancer patients. Brugnatelli, S., Gattoni, E., Grasso, D., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia: A randomized, controlled study from the "Rete Ematologica Pugliese". [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palonosetron as salvage treatment in the prevention of chemotherapy-induced nausea and vomiting in patients receiving low emetogenic chemotherapy (LEC). [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase III study of palonosetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A phase II, randomized study of aprepitant in the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Single-dose palonosetron and dexamethasone in preventing nausea and vomiting induced by moderately emetogenic chemotherapy in breast and colorectal cancer patients. [2022]