Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00977600
Recruitment Status : Completed
First Posted : September 16, 2009
Last Update Posted : January 16, 2017
Sponsor:
Collaborator:
Ucyclyd Pharma, Inc.
Information provided by:
Horizon Pharma Ireland, Ltd., Dublin Ireland

Tracking Information
First Submitted Date  ICMJE September 15, 2009
First Posted Date  ICMJE September 16, 2009
Last Update Posted Date January 16, 2017
Study Start Date  ICMJE March 2005
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 15, 2009)
The rate of adverse events [ Time Frame: 33 Days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
Official Title  ICMJE A Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
Brief Summary 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.
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • 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.
  • Drug: Ammonul
  • Drug: Buphenyl
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 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.
    Intervention: Drug: 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.
    Intervention: 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.
    Intervention: Drug: Buphenyl
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 15, 2009)
24
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2005
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ukraine
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00977600
Other Study ID Numbers  ICMJE UP 1204-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Horizon Pharma Ireland, Ltd., Dublin Ireland
Collaborators  ICMJE Ucyclyd Pharma, Inc.
Investigators  ICMJE
Principal Investigator: Igor Zupanets, MD The National University of Pharmacy
PRS Account Horizon Pharma Ireland, Ltd., Dublin Ireland
Verification Date June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP