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

A Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)

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.

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.

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