Single-dose PK Assessment of Oral Proglumide in Those With Hepatic Impairment (HIPK)
Primary Purpose
Cirrhosis, Liver
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Proglumide
Sponsored by
About this trial
This is an interventional other trial for Cirrhosis, Liver
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
Sites / Locations
- Georgetown University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Control
Hepatic Impaired
Arm Description
Healthy controls Proglumide 400 mg given once by mouth
Cirrhosis Child-Pugh A and B Proglumide 400 mg given once by mouth
Outcomes
Primary Outcome Measures
Proglumide blood levels in hepatic impaired subjects
Proglumide levels in ng/ml in cirrhosis subjects compared to healthy controls
Secondary Outcome Measures
Urinary excretion of proglumide
Measurement of proglumide in urine after single does ingestion in cirrhosis compared to healthy controls
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04814602
Brief Title
Single-dose PK Assessment of Oral Proglumide in Those With Hepatic Impairment
Acronym
HIPK
Official Title
Single-dose Pharmacokinetic (PK) Assessment of Oral Proglumide in Those With Hepatic Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
March 30, 2021 (Actual)
Primary Completion Date
August 30, 2021 (Actual)
Study Completion Date
February 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Liver
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
open labeled
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Healthy controls Proglumide 400 mg given once by mouth
Arm Title
Hepatic Impaired
Arm Type
Experimental
Arm Description
Cirrhosis Child-Pugh A and B Proglumide 400 mg given once by mouth
Intervention Type
Drug
Intervention Name(s)
Proglumide
Other Intervention Name(s)
Milid
Intervention Description
CCK receptor antagonist
Primary Outcome Measure Information:
Title
Proglumide blood levels in hepatic impaired subjects
Description
Proglumide levels in ng/ml in cirrhosis subjects compared to healthy controls
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Urinary excretion of proglumide
Description
Measurement of proglumide in urine after single does ingestion in cirrhosis compared to healthy controls
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill P Smith, MD
Organizational Affiliation
Georgetown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Will be published and placed on clinicaltrials website
Learn more about this trial
Single-dose PK Assessment of Oral Proglumide in Those With Hepatic Impairment
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