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

This study has been completed.
Sponsor:
Collaborator:
Ucyclyd Pharma Inc.
Information provided by:
Hyperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00986895
First received: September 15, 2009
Last updated: September 28, 2009
Last verified: September 2009
  Purpose

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.


Condition Intervention Phase
Hepatic Encephalopathy
Urea Cycle Disorders
Drug: HPN-100
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hyperion Therapeutics, Inc.:

Primary Outcome Measures:
  • The rate of adverse event [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: September 2006
Study Completion Date: June 2007
Intervention Details:
    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.
    Other Name: HPN-100
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00986895

Locations
Ukraine
Department of General Surgery #2; Kharkiv State Medical University
Kharkiv, Ukraine, 61128
National University of Pharmacy
Kharkiv, Ukraine, 61057
Sponsors and Collaborators
Hyperion Therapeutics, Inc.
Ucyclyd Pharma Inc.
Investigators
Principal Investigator: Igor Zupanets, MD National University of Pharmacy
  More Information

No publications provided by Hyperion Therapeutics, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00986895     History of Changes
Other Study ID Numbers: UP 1204-002
Study First Received: September 15, 2009
Last Updated: September 28, 2009
Health Authority: United States: Food and Drug Administration
Ukraine: Ministry of Health

Keywords provided by Hyperion Therapeutics, Inc.:
HPN-100
GT4P
Glyceryl tri-(4-phenylbutyrate)

Additional relevant MeSH terms:
Hepatic Encephalopathy
Urea Cycle Disorders, Inborn
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Hepatic Insufficiency
Liver Diseases
Liver Failure
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
4-phenylbutyric acid
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014