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

Hepatic Encephalopathy Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00986895
• Other study ID #: UP 1204-002
• Status: Completed
• Phase: Phase 1
• First received: September 15, 2009
• Last updated: January 13, 2017
• Start date: September 2006
• Est. completion date: June 2007

Study information

• Verified date: September 2009
• Source: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy
• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

Intervention

Drug:
• HPN-100
HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbuteric acid (PBA). PBA is converted to phenylacetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (~17.4mL) delivers an equivalent amount of PBA to40 tablets of NaPBA.

Locations

Country	Name	City	State
Ukraine	Department of General Surgery #2; Kharkiv State Medical University	Kharkiv
Ukraine	National University of Pharmacy	Kharkiv

Sponsors (2)

Lead Sponsor	Collaborator
Horizon Pharma Ireland, Ltd., Dublin Ireland	Ucyclyd Pharma, Inc.

Country where clinical trial is conducted

Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of adverse event