Ulcerative Colitis > PALI-2108 > Paid

PALI-2108 for Ulcerative Colitis

Recruiting in Palo Alto (17 mi)

Overseen By Mitchell L Jones, MD, PhD

Age: 18 - 65

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Palisade Bio

Trial Summary

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.

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.

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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

I am a man who either uses contraception or am surgically sterile.

I am a woman who cannot become pregnant due to surgery or being postmenopausal.

I am between 18 and 60 years old.

Exclusion Criteria

I have a history of kidney disease.

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

I have not had major surgery in the last 4 weeks.

I have had tuberculosis in the past.

I have recently taken PALI-2108 or another investigational drug.

I am currently pregnant or breastfeeding.

I have or had serious stomach, liver, or kidney disease.

I have not received a live vaccine in the last 4 weeks.

I am not on maintenance therapy and have no history of drug or alcohol abuse.

I have UC and have failed biologic treatments or used them recently, and may have had specific surgeries or liver issues.

Participant Groups

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.

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.

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Altasciences Montreal, Canada

Who is running the clinical trial?

Palisade Bio Lead Sponsor

Altasciences Company Inc. Industry Sponsor

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] Label="BACKGROUND">Compared with older 5-HT3 receptor antagonists, palonosetron requires fewer drug administrations to prevent chemotherapy-induced nausea and vomiting (CINV) following multiple-day chemotherapy. We conducted a phase II multicenter study comparing palonosetron plus aprepitant to palonosetron alone in patients undergoing a range of induction chemotherapy regimens for acute myeloid leukemia (AML).

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] The purpose of this study is to evaluate the efficacy and safety of intravenous (IV) palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who had incomplete control of CINV during their previous cycle of low emetogenic chemotherapy (LEC).

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

Phase III study of palonosetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients. [2021] Palonosetron has demonstrated non-inferiority to ondansetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients in the United States and Europe. We conducted a single-arm registration study to evaluate the efficacy, safety and pharmacokinetics of palonosetron in pediatric patients in Japan.

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] The present study aimed to study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer (CRC), and comprised a multicenter, phase II, open-label, randomized, parallel comparative study conducted as part of the Kagoshima aprepitant study for colon cancer in Japan. Patients with advanced or recurrent CRC were treated with standard MEC regimens (FOLFOX, XELOX or FOLFIRI) and received either standard chemotherapy [5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) + dexamethasone] or aprepitant regimen chemotherapy (5-HT3 RA + reduced-dose dexamethasone + aprepitant). The primary endpoint of the present study was the proportion of patients who achieved a complete response (CR) during the overall, acute, and delayed phases of the first planned chemotherapy cycle. Secondary endpoints were complete protection, the proportions of patients without emetic episodes or nausea, patients with no more than moderate nausea during the overall, acute and delayed phases, and the time to treatment failure. The CR rates in the overall, acute and delayed phases were similar in the aprepitant and the standard-regimen groups. Additionally, there were no significant differences in secondary endpoints between the two groups. In summary, aprepitant in combination with 5-HT3 RA and reduced-dose corticosteroids was well tolerated and effective in preventing CINV associated with moderately emetogenic antitumor agents in Japanese patients with CRC.

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] Palonosetron, a unique second-generation 5-HT3 receptor antagonist, has been demonstrated to control emesis related to chemotherapy-induced nausea and vomiting (CINV). The aim of this study was to evaluate the efficacy and tolerability of palonosetron followed by a single dose of dexamethasone in patients with breast cancer (BC) or colorectal cancer (CRC) receiving moderate emetogenic chemotherapy (MEC).