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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cirrhosis, Liver

Intervention / Treatment
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* Drug: Proglumide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: open labeled
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Healthy controls Proglumide 400 mg given once by mouth | Drug: Proglumide<br>* CCK receptor antagonist<br>* Other names: Milid;|
| Experimental: Hepatic Impaired<br>Cirrhosis Child-Pugh A and B Proglumide 400 mg given once by mouth | Drug: Proglumide<br>* CCK receptor antagonist<br>* Other names: Milid;|

What is the study measuring?
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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 |