Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children With Urea Cycle Disorders

This is an interventional treatment trial for Urea Cycle Disorders focused on measuring Urea Cycle Disorder, UCD, GT4P, Buphenyl, hyperammonemia, sodium phenylbutyrate Read More

Inclusion Criteria:

• Male and female subjects 6-17 years old.
• Signed informed consent by subject's legally acceptable representative and assent by subject, as applicable.
• Diagnosis of urea cycle disorder (enzyme or transporter deficiency) confirmed via enzymatic, biochemical, or genetic testing.

• On a stable dose of NaPBA for a diagnosis of UCD for at least 1 week prior to the Day 1 visit.

  *Subjects who are not on a stable dose of NaPBA at the initial screening visit may be converted to a stable dose of NaPBA during the screening period and enrolled as long as they are on a stable dose of NaPBA at least 1 week prior to Day 1

• Able to perform and comply with study activities, including blood draws and urine collections.
• Negative pregnancy test for all females of childbearing potential.
• All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study.

Exclusion Criteria:

• Screening ammonia level of ≥100 μmol/L or signs and symptoms indicative of hyperammonemia; subjects may be re-screened after their ammonia is controlled, at the discretion of the investigator.
• History of 4 or more hyperammonemic events as defined in Section 3.5.1 in the preceding 12 months.
• 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 CTCAE v3.0, except Grade 3 elevations in liver enzymes, defined as levels 5-20 times ULN in ALT/SGPT, aspartate aminotransferase (AST/SGOT), 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.
• Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication known to increase ammonia levels (e.g., valproate), within the 24 hours prior to Day 1 and throughout the study.
• History of QTc interval prolongation or QTc interval > 450 msec at screening or baseline.
• Known hypersensitivity to PAA or PBA.
• Liver transplant, including hepatocellular transplant.
• Currently treated with sodium benzoate or Carbaglu® (carglumic acid). At the discretion of the investigator, subjects on sodium benzoate who are otherwise eligible to participate may be switched to 100% NaPBA during the 30 day screening period as part of the study, and at least 7 days prior to Day 1 (Visit 2).
• Breastfeeding or lactating females.