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

NCT00977600 | Completed Phase 1

• 1 other identifier: UP 1204-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Ammonul; Sodium phenylacetate; sodium benzoate; Buphenyl; sodium phenylbutyrate; HPN-100; GT4P; Glyceryl tri-(4-phenylbutyrate); Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• The rate of adverse events

  33 Days

Study Arms (4)

GT4P-F

EXPERIMENTAL

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

GT4P-API

EXPERIMENTAL

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

Ammonul

ACTIVE COMPARATOR

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

Buphenyl

ACTIVE COMPARATOR

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

Interventions

HPN-100 DRUG

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.

GT4P-API; GT4P-F

Ammonul DRUG

Ammonul

Buphenyl DRUG

Buphenyl

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead
• Ucyclyd Pharma, Inc.: collaborator

Study Sites (1)

Medical Sanitary Division #2

Kharkiv, 61011, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 20512995 DERIVED

MeSH Terms

Interventions

glycerol phenylbutyrate; ammonul; 4-phenylbutyric acid

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2009
• First Posted: September 16, 2009
• Study Start: March 1, 2005
• Study Completion: July 1, 2005
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

UA (1)