Clinical trial NCT04814602: Single-dose PK Assessment of Oral Proglumide in Those With Hepatic Impairment
Official title: Single-dose Pharmacokinetic (PK) Assessment of Oral Proglumide in Those With Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Cirrhosis, Liver
Lead sponsor: Georgetown University
Sponsor class: OTHER
First posted: 2021-03-24
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: open labeled
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proglumide blood levels in hepatic impaired subjects
timeFrame: 24 hours
Secondary outcomes:
measure: Urinary excretion of proglumide
timeFrame: 24 hours
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
Study officials:
affiliation: Georgetown University
name: Jill P Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: