Study of the Safety of HPN (Hyperion)-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)

Inclusion Criteria:

• Male and female subjects who completed HPN-100-006:

*Additionally, approximately 20 UCD subjects ≥ 6 years of age may be enrolled whohave not participated in HPN-100-006. These subjects may include those who did notqualify HPN-100-006 (e.g., subjects between the ages of 6-17 years, subjects withother UCD subtypes, or adult subjects who have not taken sodium phenylbutyrate (NaPBA) in the past 6 months, etc.). For adult subjects not receiving NaPBA in thepast 6 months, subjects must, in the judgment of the investigator, be anticipated tobenefit from the addition of a nitrogen-scavenging agent to their current treatment.Clinical evidence of potential benefit from introduction of an ammonia-scavengingagent might include a recent history (in the past year) of clinically overthyperammonemia accompanied by a venous ammonia ≥ 100 μmol/L, a recent history (within the past year) of protein intolerance, or a history of abnormally highvenous ammonia levels accompanied by symptoms (e.g., headache) that might reasonablybe attributed to hyperammonemia.

• Signed informed consent by subject and/or subject's legally acceptablerepresentative.

• Diagnosis of urea cycle disorder (enzyme or transporter deficiency) confirmed viaenzymatic, biochemical, or genetic testing.

• Able to perform and comply with study activities, including blood draws.

• Negative pregnancy test for all females of childbearing potential.

• All females of childbearing potential and all sexually active males must agree touse an acceptable method of contraception throughout the study.

Exclusion Criteria:

• Screening venous ammonia level of ≥ 100 μmol/L or signs and symptoms indicative ofhyperammonemia; subjects may be re-screened after their venous ammonia iscontrolled, at the discretion of the investigator.

• History of 4 or more hyperammonemic events as defined in Section 3.5.1 in thepreceding 12 months.

• Active infection (viral or bacterial) or any other condition that may increasevenous ammonia levels.

• Any clinical or laboratory abnormality or medical condition that, at the discretionof the investigator, may put the subject at increased risk by participating in thisstudy.

• Use of any medication known to significantly affect renal clearance (e.g.,probenecid) or to increase protein catabolism (e.g., corticosteroids), or othermedication known to increase venous ammonia levels (e.g., valproate), within the 24hours prior to Day 1 and throughout the study.

• History of QTc (QT interval corrected) prolongation, or a QTc interval ≥ 450 msec oran increase of ≥ 60 msec during the previous HPN-100 study if applicable.

• Known hypersensitivity to PAA or PBA.

• Liver transplant, including hepatocellular transplant.

• Breastfeeding or lactating females.