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).

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.

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

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

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.

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.