NCT03216876

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).

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Sep 2017

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 5, 2016

Completed
1.5 years until next milestone

First Posted

Study publicly available on registry

July 13, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2017

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2019

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2019

Completed
Last Updated

July 25, 2017

Status Verified

July 1, 2017

Enrollment Period

1.3 years

First QC Date

January 5, 2016

Last Update Submit

July 21, 2017

Conditions

Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (1)

  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Number of serious adverse events or Grade 3-4 biochemical abnormalities

    24 hours

Secondary Outcomes (10)

  • maximum plasma concentration (C¬max)

    24 hours

  • half-life (t1/2),

    24 hours

  • volume of distribution (Vd)

    24 hours

  • clearance

    24 hours

  • Area under the concentration-time curve (AUC)

    24 hours

  • +5 more secondary outcomes

Study Arms (3)

Healthy Controls

EXPERIMENTAL

Healthy subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg

Drug: Ursolic acid

PSC Single Dose

EXPERIMENTAL

PSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg

Drug: Ursolic acid

PSC Multiple Dose

EXPERIMENTAL

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

Drug: Ursolic acid

Interventions

Ursolic acidDRUG

Ursolic acid (UA) is a natural triterpenoid carboxylic acid, which has been studied for its anti-proliferative and anti-inflammatory activities.

Also known as: urson, prunol, malol, 3-beta-3-hydroxy-urs-12-ene-28-oic-acid
Healthy ControlsPSC Multiple DosePSC Single Dose

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Univeristy of California Davis Medical Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

Ursolic Acid

Condition Hierarchy (Ancestors)

CholangitisBile Duct DiseasesBiliary Tract DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Pentacyclic TriterpenesTriterpenesTerpenesHydrocarbonsOrganic ChemicalsSapogenins

Study Officials

  • Christopher Bowlus, MD

    University of California, Davis

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 5, 2016

First Posted

July 13, 2017

Study Start

September 1, 2017

Primary Completion

January 1, 2019

Study Completion

July 1, 2019

Last Updated

July 25, 2017

Record last verified: 2017-07

Locations

US(1)