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

Early Phase 1

Completed

• Conditions: Cirrhosis, Liver
• Interventions: Drug: Proglumide

• Registration Number: NCT04814602
• Lead Sponsor: Georgetown University

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2021-03-22
• Study First Submitted QC: 2021-03-22
• Study First Posted: 2021-03-24
• Study Start: 2021-03-30
• Status Verified: 2021-07
• Primary Completion: 2021-08-30
• Study Completion: 2022-02-20
• Last Update Submitted: 2022-03-14
• Last Update Posted: 2022-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Proglumide	Healthy controls Proglumide 400 mg given once by mouth
Hepatic Impaired	Proglumide	Cirrhosis Child-Pugh A and B Proglumide 400 mg given once by mouth

Primary Outcome Measures

Name	Time	Method
Proglumide blood levels in hepatic impaired subjects	24 hours	Proglumide levels in ng/ml in cirrhosis subjects compared to healthy controls

Secondary Outcome Measures

Name	Time	Method
Urinary excretion of proglumide	24 hours	Measurement of proglumide in urine after single does ingestion in cirrhosis compared to healthy controls

Trial Locations

Locations (1)

Georgetown University; 🇺🇸 Washington, District of Columbia, United States