This non-randomized, open-label study was approximately one year in duration and consisted of a short term NaPBA to HPN-100 switchover part involving two overnight stays followed by a 12-month long term treatment period involving monthly visits.

This was an open-label study consisting of a 10-day switch-over period during which subjects were switched from their prescribed dose of sodium phenylbutyrate (BUPHENYLTM or NaPBA) to a dose of HPN-100 that delivered the same amount of the active ingredient, PBA, followed by long-term treatment with HPN-100 for up to 12 months. The study was designed to capture information important for evaluating safety, Pharmacokinetics, and efficacy while recognizing sampling limitations in young children and current standard of care. Patients eligible for this study included pediatric patients from 29 days to < 6 years of age with either a diagnosed or clinically suspected Urea Cycle Disorders (UCD) who are receiving a stable dose of the powder formulation of NaPBA. Subjects were clinically stable and had been receiving a stable dose NaPBA powder for at least 5 days at the time of enrollment.

During the switch-over part of the study, subjects switched from NaPBA to HPN-100 in one step and had two overnight stays with 24 hour blood sampling, the first of which was on Day 1, while still taking NaPBA, and the second of which was on approximately Day 10 while taking HPN-100. Subjects then continued in the long-term treatment phase which was 12 months in duration.

Study acquired from Horizon in 2024.

Inclusion Criteria:

• Male and female subjects 29 days to < 6 years old. If the subject is born prematurely, calculation of the lower age limit begins at the corrected gestational age of 40 weeks.
• Signed informed consent by the subject's legally acceptable representative
• Suspected or confirmed UCD diagnosis of any subtype, except NAGS deficiency
• On stable dose of NaPBA powder for at least 5 days before Day 1
• Not receiving sodium benzoate for at least 5 days before Day 1
• No concomitant illness which would preclude safe participation as judged by the investigator
• Able to receive medication orally
• Has not undergone liver transplantation, including hepatocellular transplantation
• Judged sufficiently stable and compliant with diet and treatment to be suitable for enrollment

Exclusion Criteria:

• Screening ammonia level > 100 μmol/L and signs and symptoms indicative of hyperammonemia; subjects may be rescreened after their ammonia is controlled and they are clinically stable, at the discretion of the investigator
• Use of any investigational drug within 30 days of Day 1
• Active infection (viral or bacterial) or any other condition that may increase ammonia levels
• Any clinical or laboratory abnormality of Grade 3 or greater severity according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03, except Grade 3 elevations in ammonia and liver enzymes, defined as levels 5-20 times ULN (upper limit of normal)in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma glutamyl transpeptidase (GGT) in a clinically stable subject
• Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at increased risk by participating in this study
• Known hypersensitivity to PAA or PBA
• Liver transplant, including hepatocellular transplant
• Currently treated with Carbaglu® (carglumic acid)

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.