This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a fixed-sequence, open-label, Switch Over study of HPN-100 with a long-term (12- month) Safety Extension part designed to assess the safety of HPN-100 in pediatric subjects and to prospectively assess the ability of HPN-100 to control blood ammonia as compared with NaPBA. Subjects will receive NaPBA three times daily (TID) with meals during the first week and the same PBA mole-equivalent dose of HPN-100 during the second week. If there are safety concerns regarding a single-step transition from NaPBA to HPN-100, at the investigator??""""""""s discretion, the transition may occur in 2 steps such that in the second week subjects may receive 50% of the PBA equivalent dose as NaPBA and 50% as HPN-100 before receiving 100% of the PBA equivalent dose as HPN-100 in the third week. Serial blood samples will be collected for PK and blood ammonia assessments after each drug has reached steady state, which is achieved approximately 4 days after initiation of 100% NaPBA or HPN-100 treatment. Subjects who complete the Switch Over part of the study will be offered the opportunity to continue in the study by entering the Safety Extension part of the study to continue receiving open-label HPN-100 for up to 12 months. Subjects who exit the protocol after enrollment but prior to completion of the study will have all the safety assessments, including safety labs and a single blood sample drawn for measurement of phenylbutyrate (PBA), the active metabolite phenylacetate (PAA), and the terminal metabolite phenylacetylglutamine (PAGN). The time of day at which the blood sample is drawn will be recorded as well as the time since the last dose of medication was taken. Subjects will follow a stable diet throughout the study as prescribed by the investigator and dietary compliance will be recorded at each study visit for both the Switch Over part and Safety Extension part of the study.
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