Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)

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)