An Open-Label Study Of Ursolic Acid For Primary Sclerosing Cholangitis
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Study Overview
Brief Summary
This is an open-label, active treatment trial to determine the pharmacokinetics of orally administered ursolic acid and to assess the potential efficacy and safety of ursolic acid in subjects with primary sclerosing cholangitis (PSC).
Detailed Description
In the first phase of this trial, 6 healthy subjects and 2 PSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg to determine the optimal dose in humans.
The second phase of this trial will involve 20 PSC subjects assigned to treatment with daily oral ursolic acid at the dose determined to be optimal in the first phase of the study. The treatment will last for 24 weeks with an off-treatment follow up of 28 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female age 18 - 70 years of age
- •PSC documented by typically cholangiogram findings of strictures and dilations with no evidence of a secondary cause of sclerosing cholangitis
- •Serum alkaline phosphatase greater than 1.5 times the upper limit of the normal reference range at the UC Davis Health Systems Clinical Laboratory
- •AST and ALT ≤ 10 x ULN
- •Serum creatinine < 2.0 mg/dL
- •Mayo Activity Index of < 2 (in those with ulcerative colitis or Crohn's colitis)
- •Negative serum pregnancy test for female subjects of childbearing potential, agreement to use a highly effective method of contraception during heterosexual intercourse (females of childbearing potential), lactating females must agree to discontinue nursing before starting study treatment, and barrier contraception during heterosexual intercourse (males not vasectomized).
Exclusion Criteria
- •Pregnancy
- •Hepatic decompensation defined as ascites (or use of diuretics), episodes of hepatic encephalopathy, variceal bleeding or an INR > 1.2
- •Positive HCV RNA or HBsAg, positive anti-mitochondrial antibody, alcohol consumption greater than 21oz/week for males or 14oz/week for females
- •Clinically significant cardiac disease, history of cholangiocarcinoma, history of liver transplantation, history of cancers, other than non-melanomatous skin cancer, within 5 years prior to screening
- •Ascending cholangitis within 60 days of screening
- •Use of immunosuppressants including 6-mercaptopurine, azathioprine, methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and anti-TNF or other biologics within 6 months of enrollment
- •Use of antibiotics including vancomycin, metronidazole, or rifaximin within 60 days of enrollment
Arms & Interventions
Healthy Controls
Healthy subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg
Intervention: Ursolic acid (Drug)
PSC Single Dose
PSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg
Intervention: Ursolic acid (Drug)
PSC Multiple Dose
PSC subjects assigned to treatment with daily oral ursolic acid at the dose determined to be optimal in the first phase of the study. The treatment will last for 24 weeks with an off-treatment follow up of 28 weeks
Intervention: Ursolic acid (Drug)
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 24 hours
Number of serious adverse events or Grade 3-4 biochemical abnormalities
Secondary Outcomes
- volume of distribution (Vd)(24 hours)
- C-reactive Protein (CRP)(24 weks)
- Biochemical response(24 weeks)
- Alanine aminotransferase (ALT)(24 weeks)
- maximum plasma concentration (C¬max)(24 hours)
- half-life (t1/2),(24 hours)
- clearance(24 hours)
- Area under the concentration-time curve (AUC)(24 hours)
- Total bilirubin(24 weks)
- Mayo Risk Score (MRS)(24 weks)