Hepatic Encephalopathy, Urea Cycle Disorders
Conditions
Keywords
HPN-100, GT4P, Glyceryl tri-(4-phenylbutyrate)
Brief summary
The purpose of this study is to determine the safety and tolerability of GT4P administered orally as a single dose, and twice daily for 7 consecutive days, to subjects with hepatic impairment with cirrhosis (Child-Pugh scores of A, B, or C) and to a gender matched and similar age control group with normal hepatic function.
Detailed description
Study acquired from Horizon in 2024.
Interventions
DRUGHPN-100
HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. HPN-100 is broken down to phenylbuteric acid (PBA). PBA is converted to phenylacetic acid (PAA) that is the active metabolite. Three teaspoons of HPN-100 (\ 17.4mL) delivers an equivalent amount of PBA to40 tablets of NaPBA.
Sponsors
Ucyclyd Pharma, Inc.
Amgen
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects were required to fulfill the following criteria in order to participate in the study: Screening: * Males or females aged ≥ 18 years of age * Able 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 * Classification to one of the following: * current diagnosis of hepatic impairment with cirrhosis * healthy subject * Subjects with hepatic impairment with cirrhosis were classifiable to one of the following groups: * Child-Pugh score A * Child-Pugh score B * Child-Pugh score C * Subjects with hepatic impairment with cirrhosis who were on a therapeutic regimen of lactulose must have been on a stable dose for ≥ 30 days prior to screening * If female, a negative pregnancy test at screening and pre-dose on day 0, or a documented sterilization procedure; a female of child-bearing potential must have been using a medically approved birth control method and must have agreed to use the same method of contraception during the full course of the study (on pre-dose day 0 as well as at screening) * Weight within the range of 60-100 kg (at screening and pre-dose on day 0) * Willing to stop taking any medication that the Sponsor and the Investigator felt was not appropriate for use during the study, beginning 2 days before dosing and throughout the study
Exclusion criteria
Subjects who fulfilled any of the following criteria were excluded from the study: Screening: * Clinically significant history or evidence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), as determined by the Investigator * Serum sodium \< 120 mEq/L * Serum creatinine ≥ 1.5 upper limit of normal * Potassium ≤ 3.5 mEq/L * Other laboratory values outside the normal range which were determined to be clinically significant by the Investigator * Significant illness within the last 14 days * Oral temperature \> 38.5°C or \< 36°C and/or a suspected site of active infection * Inflammatory bowel disease or malabsorption defined with steatorrhea * Active gastrointestinal bleeding, defined as melena, hematochezia, or hematemesis requiring hospitalization within the last 30 days * Use of probenecid, valproate, or corticosteroids within the last 24 hours * Use of any medication, other than those approved by the Sponsor and Investigator, in the last 48 hours * History of seizures within the last 72 hours * Positive drugs of abuse urine test * Positive alcohol breath test * Donation or loss of blood (500 mL or more) within the last 30 days * Donation or loss of plasma within the last 7 days * History of acquired immunodeficiency syndrome (AIDS) or determined human immunodeficiency virus (HIV) positive * Hepatitis B or C (HBV; HCV) positive (healthy volunteers only) * Use of any investigational drug within the last 30 days * Known hypersensitivity to sodium phenylbutyrate or similar drugs * Emergency hospitalization within the last 90 days * Intake of alcohol in the last 7 days Pre-dose (days 0 and 7): * Significant illness or emergency hospitalization since the last study visit * Oral temperature \> 38.5°C or \< 36°C and/or a suspected site of active infection * Use of probenecid, valproate, or corticosteroids within the last 24 hours * Use of any non-approved medication (by the Sponsor/Investigator) within the 48 hours before dosing * History of seizures within the last 72 hours * Positive drugs of abuse urine test * Positive alcohol breath test * Donation or loss of blood (500 mL or more) or plasma since the last study visit * Use of any investigational drug since the last study visit * Intake of alcohol in the last 7 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rate of adverse event | — |
Countries
Ukraine
Outcome results
None listed