A Study of Glyceryl Tri-(4-phenylbutyrate) Administered Orally as a Single Dose, and Twice Daily for Seven Consecutive Days to Subjects With Hepatic Impairment With Cirrhosis and to a Control Group

Phase 1

Completed

• Conditions: Urea Cycle Disorders; Hepatic Encephalopathy

• Registration Number: NCT00986895
• Lead Sponsor: Amgen

Brief Summary

The purpose of this study is to determine the safety and tolerability of GT4P administered orally as a single dose, and twice daily for 7 consecutive days, to subjects with hepatic impairment with cirrhosis (Child-Pugh scores of A, B, or C) and to a gender matched and similar age control group with normal hepatic function.

Detailed Description

Study acquired from Horizon in 2024.

Study Timeline

• Study Start: 2006-09
• Study Completion: 2007-06
• Study First Submitted: 2009-09-15
• Study First Submitted QC: 2009-09-28
• Study First Posted: 2009-09-30
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-18
• Last Update Posted: 2024-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Subjects were required to fulfill the following criteria in order to participate in the study:

Screening:

• Males or females aged ≥ 18 years of age

• Able to provide written informed consent before any study-related procedures, and ability, in the opinion of the Investigator, to comply with all the requirements of the study

• Classification to one of the following:

  • current diagnosis of hepatic impairment with cirrhosis
  • healthy subject

• Subjects with hepatic impairment with cirrhosis were classifiable to one of the following groups:

  • Child-Pugh score A
  • Child-Pugh score B
  • Child-Pugh score C

• Subjects with hepatic impairment with cirrhosis who were on a therapeutic regimen of lactulose must have been on a stable dose for ≥ 30 days prior to screening

• If female, a negative pregnancy test at screening and pre-dose on day 0, or a documented sterilization procedure; a female of child-bearing potential must have been using a medically approved birth control method and must have agreed to use the same method of contraception during the full course of the study (on pre-dose day 0 as well as at screening)

• Weight within the range of 60-100 kg (at screening and pre-dose on day 0)

• Willing to stop taking any medication that the Sponsor and the Investigator felt was not appropriate for use during the study, beginning 2 days before dosing and throughout the study

Exclusion Criteria

Subjects who fulfilled any of the following criteria were excluded from the study:

Screening:

• Clinically significant history or evidence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), as determined by the Investigator
• Serum sodium < 120 mEq/L
• Serum creatinine ≥ 1.5 upper limit of normal
• Potassium ≤ 3.5 mEq/L
• Other laboratory values outside the normal range which were determined to be clinically significant by the Investigator
• Significant illness within the last 14 days
• Oral temperature > 38.5°C or < 36°C and/or a suspected site of active infection
• Inflammatory bowel disease or malabsorption defined with steatorrhea
• Active gastrointestinal bleeding, defined as melena, hematochezia, or hematemesis requiring hospitalization within the last 30 days
• Use of probenecid, valproate, or corticosteroids within the last 24 hours
• Use of any medication, other than those approved by the Sponsor and Investigator, in the last 48 hours
• History of seizures within the last 72 hours
• Positive drugs of abuse urine test
• Positive alcohol breath test
• Donation or loss of blood (500 mL or more) within the last 30 days
• Donation or loss of plasma within the last 7 days
• History of acquired immunodeficiency syndrome (AIDS) or determined human immunodeficiency virus (HIV) positive
• Hepatitis B or C (HBV; HCV) positive (healthy volunteers only)
• Use of any investigational drug within the last 30 days
• Known hypersensitivity to sodium phenylbutyrate or similar drugs
• Emergency hospitalization within the last 90 days
• Intake of alcohol in the last 7 days

Pre-dose (days 0 and 7):

• Significant illness or emergency hospitalization since the last study visit
• Oral temperature > 38.5°C or < 36°C and/or a suspected site of active infection
• Use of probenecid, valproate, or corticosteroids within the last 24 hours
• Use of any non-approved medication (by the Sponsor/Investigator) within the 48 hours before dosing
• History of seizures within the last 72 hours
• Positive drugs of abuse urine test
• Positive alcohol breath test
• Donation or loss of blood (500 mL or more) or plasma since the last study visit
• Use of any investigational drug since the last study visit
• Intake of alcohol in the last 7 days

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The rate of adverse event

Trial Locations

Locations (2)

Department of General Surgery #2; Kharkiv State Medical University; 🇺🇦 Kharkiv, Ukraine

National University of Pharmacy; 🇺🇦 Kharkiv, Ukraine