Efficacy and Safety of HPN-100 for the Treatment of Adults With Urea Cycle Disorders

Exclusion Criteria

• •Screening or baseline ammonia level of ≥ 100 μmol/L or signs and symptoms indicative of hyperammonemia during the 2-week period preceding screening or enrollment; subjects may be re-screened after their ammonia is controlled and are stable for at least 14 days, 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 intercurrent condition (apart from UCD) 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) v3.0, except Grade 3 elevations in liver enzymes, defined as levels 5-20 times upper limit of normal (ULN) in alanine aminotransferase (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
• •Use of sodium benzoate within one week of Day 1
• •History of corrected QT interval (QTc) prolongation or QTc interval \> 450 msec at screening or baseline
• •Known hypersensitivity to phenylacetate (PAA) or phenylbutyrate (PBA)
• •Liver transplant, including hepatocellular transplant
• •Breastfeeding or lactating females