Drug Toxicity
Conditions
Brief summary
Arm 1: Primary Objective: • To determine the safety and tolerability of multiple ascending, supratherapeutic doses of HPN-100. Arm 2: Primary Objective: • To assess the effects of steady-state levels of HPN-100 metabolites (4 phenylbutyric acid \[PBA\], phenylacetic acid \[PAA\], and phenylacetylglutamine \[PAGN\]) on 12-lead electrocardiogram (ECG) parameters in healthy male and female subjects with the primary endpoint being the time-matched change from baseline in the QT interval corrected for heart rate (HR) based on an individual correction method (QTcI).
Detailed description
Assess the effects of steady-state levels of HPN-100 metabolites (4-phenylbutryic acid (PBA), phenylacetic acid (PAA), and phenylacetylglutamine (PAGN) on 12-lead electrocardiogram (ECG) parameters in health male and female subjects with the primary endpoint being the time-matched change from baseline in the QT interval corrected for heart rate(HR) based on an individual correction method (QTcl). Study acquired from Horizon in 2024.
Interventions
DRUGHPN-100
single oral dose of 9 mL HPN-100 given via syringes 3 times daily for 3 days
DRUGHPN-100 or Placebo
single oral dose of 12 mL HPN-100 given via syringes 3 times daily for 3 days
DRUGPlacebo
single oral (by mouth) dose of 9 mL placebo given via syringes 3 times daily for 3 days
DRUGMoxifloxacin
single oral 400-mg dose on study Day 3
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be in good health * Negative hepatitis panel and negative HIV antibody screens * Females must be non-pregnant, non-lactating, and either postmenopausal or agree to to use adequate contraceptive methods throughout the study * Males must either be sterile or willing to use adequate contraceptive methods throughout the study * Willing and able to comply with all trial requirements * Able to comprehend and willing to sign an Informed Consent Form (ICF)
Exclusion criteria
* History or clinical manifestations of significant allergic, metabolic, hepatic, renal, endocrine, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders * History of hypersensitivity or allergies to any drug compound * History of stomach or intestinal surgery or resection * History or presence of an abnormal ECG * History of alcoholism or drug addiction within 1 year * Use of any tobacco-containing or nicotine-containing products within 3 months * Participated in any other clinical trial of an investigational drug (or a medical device) within 30 days * Use of any prescription medications/products other than contraceptives within 14 days * Use of any over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days * Test positive for drug(s) of abuse, ethanol, or cotinine * Have donated blood or blood components within 30 days * Have received blood products within 2 months * Have a history of unexplained syncope * Have a family history of unexplained sudden death
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability as measured by the rate and severity of adverse events in each treatment group. | 3-day treatment period |
| Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN | 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments |
Secondary
| Measure | Time frame |
|---|---|
| Correlate time-matched ECG waveform changes to steady-state levels of HPN-100 by using QTcB and QTcF formulas to assess ECG morphologic changes. | 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments |
| Correlate time-matched QTcI change from baseline and serum levels of PBA, PAA, and PAGN drawn on Day 1, Day 2, Day 3, and Day 4 | 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments |
| Gender differences in metabolism of HPN-100 as measured by time-matched serum levels of HTN-100, PBA, PAA, and PAGN via samples drawn on Day 1, Day 2, Day 3, and Day 4. | 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments |
| Number and severity of adverse events in each treatment group. | 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments |
Countries
United States
Outcome results
None listed