Single-dose PK Assessment of Oral Proglumide in Those With Hepatic Impairment

Cirrhosis, Liver Clinical Trial

— HIPK  

Official title:

Single-dose Pharmacokinetic (PK) Assessment of Oral Proglumide in Those With Hepatic Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04814602
• Other study ID #: 3464
• Status: Completed
• Phase: Early Phase 1
• Start date: March 30, 2021
• Est. completion date: February 20, 2022

Study information

• Verified date: July 2021
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Proglumide is an oral cholecystokinin (CCK) receptor antagonist that has been shown in non-clinical studies to reverse hepatic fibrosis and decrease the incidence of hepatocellular carcinoma (HCC). Because of these potential beneficial properties, proglumide may be useful in decreasing the fibrosis and risk for HCC in those with cirrhosis. Although proglumide is safe in those with normal hepatic function, the pharmacokinetics have not been established in those that are hepatic impaired. The purpose of this study is to analyze proglumide blood levels and excretion in subjects with cirrhosis compared to health controls.

Description:

The purpose of this study is to measure blood levels of proglumide after a single oral dose (400 mg) over a period of time and compare the blood levels to those with normal hepatic function (N=4) to determine if there is delayed metabolism and clearance of proglumide in those with hepatic impairment (HI) (N=8). Eligible subjects will provide a baseline blood and urine sample prior to ingesting proglumide 400 mg po. Blood will be collected from an intravenous catheter after ingestion at the following intervals: 1 hr, 3 hrs, 5 hrs, 7 hrs and 24 hr (± 4-5 hours). After 3 hrs and 5 hrs subjects will provide a urine sample. Samples will be analyzed by Mass Spectometry. Proglumide blood and urine levels in ng/ml will be plotted over time and the Cmax (peak plasma concentration), Tmax (time to reach Cmax) and T1/2 (elimination half time) calculated for each subject and compared to that of 4 healthy controls.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: February 20, 2022
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cirrhosis previously confirmed by one of the following: Liver biopsy, FibroScan, FibroSure, MR-Elastography, or nodular liver on radiographic imaging like CT or MRI. Child-Pugh classification A (N=4) and Child-Pugh classification B (N=4)

Exclusion Criteria:

• Those that are Child-Pugh classification C cirrhosis

• gastrointestinal bleeding from esophageal varices within 6 months

• Chronic kidney disease with Estimated glomerular filtration rate (eGFR of < 90 mL/min/1.73m2)

• hepatic encephalopathy

• those that have had an organ transplant

• active hepatitis C, active hepatitis B, and those with HIV disease

• Adults unable to consent

• Individuals who are not yet adults (infants, children, teenagers)

• Pregnant women

• Prisoners

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Liver Cirrhosis

Intervention

Drug:
• Proglumide
CCK receptor antagonist

Locations

Country	Name	City	State
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Georgetown University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proglumide blood levels in hepatic impaired subjects	Proglumide levels in ng/ml in cirrhosis subjects compared to healthy controls	24 hours
Secondary	Urinary excretion of proglumide	Measurement of proglumide in urine after single does ingestion in cirrhosis compared to healthy controls	24 hours