Clinical trial NCT00977600: A Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
Official title: A Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Ammonul
Sodium phenylacetate
sodium benzoate
Buphenyl
sodium phenylbutyrate
HPN-100
GT4P
Glyceryl tri-(4-phenylbutyrate)
Healthy Volunteers
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Ucyclyd Pharma, Inc.
First posted: 2009-09-16
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 acquired from Horizon in 2024.

Eligibility 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

Primary outcomes:
measure: The rate of adverse events
timeFrame: 33 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Kharkiv
country: Ukraine
facility: Medical Sanitary Division #2
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.