A Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)

This study has been completed.
Sponsor:
Collaborator:
Ucyclyd Pharma Inc.
Information provided by:
Hyperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00977600
First received: September 15, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  Purpose

To determine the safety and tolerability of single oral doses of HPN-100 as a formulation (GT4P-F) and GT4P as the active pharmaceutical ingredient (GT4P-API) administered to healthy male subjects.


Condition Intervention Phase
Healthy
Drug: HPN-100
Drug: Ammonul
Drug: Buphenyl
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The rate of adverse events [ Time Frame: 33 Days ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: March 2005
Study Completion Date: July 2005
Arms Assigned Interventions
Experimental: GT4P-F
GT4P-F (80% GT4P) was supplied as an odorless, colorless, tasteless liquid oil in 125 ml bottles. This formulation was designed to be mixed in water and create a self-emulsifying suspension, thus administered in water for the trial. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-F was mixed in 50 ml of water, taken orally, and then the cup rinsed with 50 ml of water and taken orally. GT4P-F was stored at ambient temperature away from light.
Drug: HPN-100
HPN-100 is a triglyceride that has a similar mechanism of action as Buphenyl. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbutyric acid (PBA). PBA is converted to phenyl acetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (~17.4mL) delivers equivalent amount of PBA that 40 tablets of NaPBA do.
Other Name: HPN-100
Experimental: GT4P-API
GT4P-API was supplied as an odorless, colorless, tasteless oil in 125 ml bottles. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-API was taken orally and washed down with 100 ml of water. GT4P-API was stored at ambient temperature, away from light.
Drug: HPN-100
HPN-100 is a triglyceride that has a similar mechanism of action as Buphenyl. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbutyric acid (PBA). PBA is converted to phenyl acetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (~17.4mL) delivers equivalent amount of PBA that 40 tablets of NaPBA do.
Other Name: HPN-100
Active Comparator: Ammonul
Ammonul® was supplied as single-use glass vials of 10% sodium phenylacetate and 10% sodium benzoate for intravenous injection. Ammonul® was diluted before use with sterile dextrose injection 10% to a concentration of 9 mg/ml. Once diluted it was kept at room temperature and used within 24 hours. The dose was 2.75 g/m2 and was administered as an intravenous infusion over a 120-minute period. Ammonul® was stored at 25°C, within a range of 15-30°C.
Drug: Ammonul
Active Comparator: Buphenyl
Sodium phenylbutyrate or Buphenyl® was supplied as a white powder in 250 g bottles. The required amount of powder (equivalent to 3 g/m2 of PBA) was weighed out, mixed in 100 ml of water, and administered orally. Doses were calculated on a weight/volume basis and corrected for sodium content and purity. Buphenyl® was stored at ambient temperature.
Drug: Buphenyl

Detailed Description:

A randomized, open-label, four-treatment, four-period crossover study in which healthy male subjects received a single dose of each of the following four treatments on four separate dosing days, 7 days apart:

  • Oral sodium phenylbutyrate (Buphenyl®) equivalent to 3 g/m2 of 4-phenylbutyric acid (PBA) per dose
  • Oral GT4P-F mole equivalents to 3 g/m2 of PBA per dose
  • Oral GT4P-API mole equivalents to 3 g/m2 of PBA per dose
  • Intravenous 10% sodium phenylacetate plus 10% sodium benzoate (Ammonul®) 2.75 g/m2
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

  • Males aged 18 to 45 years of age
  • Ability 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
  • Subjects who were in good health as determined by a medical history, physical examination, serum chemistry, hematology, urinalysis, 12 lead ECG, and vital signs
  • Weight within the range of 60-120 kg

Exclusion Criteria:

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

  • Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurologic, immunologic, or psychiatric disorder(s), as determined by the investigator
  • Clinically significant abnormal laboratory values (as determined by the investigator)
  • Significant illness within 14 days prior to screening
  • Any disorder that might significantly interfere with the absorption, distribution, metabolism, or excretion of any drug
  • Use of any prescription medication within 14 days prior to screening
  • Use of dietary supplements, herbal medicines, vitamins, or over-the-counter medication(s) (with the exception of acetaminophen ≤ 500 mg/day) within 10 days prior to first dosing
  • Positive drugs of abuse urine test at screening or pre-dose day (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, methadone)
  • Positive alcohol breath test at screening or pre-dose day
  • Donation or loss of blood (500 ml or more) within 30 days prior to first dosing, or during the study
  • Donation or loss of plasma within 7 days prior to first dosing, or during the study
  • History of or current hepatitis or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HC)
  • History of acquired immunodeficiency syndrome (AIDS) or determined HIV positive at screening
  • Use of any investigational drug within 12 weeks prior to first dosing
  • Known hypersensitivity to sodium phenylbutyrate or similar drugs
  • Previous exposure to sodium phenylbutyrate
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00977600

Locations
Ukraine
Medical Sanitary Division #2
Kharkiv, Ukraine, 61011
Sponsors and Collaborators
Hyperion Therapeutics, Inc.
Ucyclyd Pharma Inc.
Investigators
Principal Investigator: Igor Zupanets, MD The 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: NCT00977600     History of Changes
Other Study ID Numbers: UP 1204-001
Study First Received: September 15, 2009
Last Updated: September 15, 2009
Health Authority: United States: Food and Drug Administration
Ukraine: Ministry of Health

Keywords provided by Hyperion Therapeutics, Inc.:
Ammonul
Sodium phenylacetate
sodium benzoate
Buphenyl
sodium phenylbutyrate
HPN-100
GT4P
Glyceryl tri-(4-phenylbutyrate)
Healthy Volunteers

Additional relevant MeSH terms:
Phenylacetic acid
4-phenylbutyric acid
Sodium Benzoate
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 15, 2014