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

Georgetown University

Status and phase

Completed

Early Phase 1

Conditions

Cirrhosis, Liver

Treatments

Drug: Proglumide

Study type

Interventional

Funder types

Other

Identifiers

NCT04814602

3464

Details and patient eligibility

About

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.

Full 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.

Enrollment

11 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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