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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy; Urea Cycle Disorders
• Intervention / Treatment: Drug: HPN-100

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Ukraine
  • Kharkiv, Ukraine, 61057
    • National University of Pharmacy
  • Kharkiv, Ukraine, 61128
    • Department of General Surgery #2; Kharkiv State Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The rate of adverse event

Collaborators and Investigators

• Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Collaborators: Ucyclyd Pharma, Inc.
• Investigators: Principal Investigator: Igor Zupanets, MD, National University of Pharmacy

Publications and helpful links

General Publications

• McGuire BM, Zupanets IA, Lowe ME, Xiao X, Syplyviy VA, Monteleone J, Gargosky S, Dickinson K, Martinez A, Mokhtarani M, Scharschmidt BF. Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis. Hepatology. 2010 Jun;51(6):2077-85. doi: 10.1002/hep.23589.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: September 15, 2009
• First Submitted That Met QC Criteria: September 28, 2009
• First Posted (Estimate): September 30, 2009

Study Record Updates

• Last Update Posted (Estimate): January 16, 2017
• Last Update Submitted That Met QC Criteria: January 13, 2017
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: GT4P; HPN-100; Glyceryl tri-(4-phenylbutyrate)
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Hepatic Encephalopathy; Brain Diseases; Urea Cycle Disorders, Inborn
• Other Study ID Numbers: UP 1204-002