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

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

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis, Liver
• Intervention / Treatment: Drug: Proglumide

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control; Healthy controls Proglumide 400 mg given once by mouth	Drug: Proglumide; CCK receptor antagonist; Other Names: Milid
EXPERIMENTAL: Hepatic Impaired; Cirrhosis Child-Pugh A and B Proglumide 400 mg given once by mouth	Drug: Proglumide; CCK receptor antagonist; Other Names: Milid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proglumide blood levels in hepatic impaired subjects	Proglumide levels in ng/ml in cirrhosis subjects compared to healthy controls	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary excretion of proglumide	Measurement of proglumide in urine after single does ingestion in cirrhosis compared to healthy controls	24 hours

Collaborators and Investigators

• Sponsor: Georgetown University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 30, 2021
• Primary Completion (ACTUAL): August 30, 2021
• Study Completion (ACTUAL): February 20, 2022

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (ACTUAL): March 24, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Gastrointestinal Agents; Anti-Ulcer Agents; Proglumide
• Other Study ID Numbers: 3464

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will be published and placed on clinicaltrials website

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No