To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs)

Long Term Use of HPN-100 in Urea Cycle Disorders

This was an open-label, long-term safety study of HPN-100 (RAVICTI; glycerol phenylbutyrate) in participants with a urea cycle disorder (UCD) who completed the safety extensions of HPN-100-005 (NCT00947544; HPN-100-005SE), HPN-100-006 (NCT00947297; HPN-100-007), or HPN-100-012 (NCT01347073; HPN-100-012SE). The initial studies were 1- to 2-week crossover studies, and their associated safety extensions were 12-month, open-label studies. All participants who completed the initial studies were eligible to enroll in the associated safety extension studies, and new participants were also permitted to enroll directly into the safety extension studies.

The duration of treatment in this study was open-ended. Participants were to return for clinic visits as prescribed by the investigator, and were to be seen at a minimum of every 6 months. At each clinic visit, participants were queried about any adverse events (AEs) or hyperammonemic crises (HACs) that occurred since the last visit. Physical and neurological examinations were performed, and blood samples were collected for the analysis of ammonia, amino acid panels, and routine clinical laboratory safety tests. Participants underwent neuropsychological testing at baseline, every 12 months thereafter, and at the final study visit.

Study acquired from Horizon in 2024.

Inclusion Criteria:

• Male and female subjects who completed Studies HPN-100-005SE, HPN-100-007, or HPN-100-012SE
• Signed informed consent by participant and/or participant's legally authorized representative
• Negative pregnancy test for all females of childbearing potential

Exclusion Criteria:

• Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may have put the participant at increased risk when participating
• Known hypersensitivity to PAA (phenylacetate) or PBA (phenylbutyrate).
• Liver transplant, including hepatocellular transplant
• Pregnant, breastfeeding or lactating females