Principal Investigator: Nicola Longo
Keywords: Urea cycle disorders , Ravicti Department: Pediatric Genetics
IRB Number: 00083717 Co Investigator:  
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Not yet recruiting

Contact Information

Carrie Bailey

Brief Summary

To assess safety, ammonia control and pharmacokinetics of RAVICTI Oral Liquid for treatment of pediatric subjects up to 2 years of age with Urea Cycle disorders (UCDs).
Study Purpose
RAVICTI is indicated for treatment of patients with UCDs. However, there are no clinical data on the use of RAVICTI in patients less than 2 months of age, for which RAVICTI is contraindicated. This study will evaluate safety and efficacy of Ravicti in patients with urea cycle disorders up to 2 years of age including patients in the first two months of life.
Children less than 2 months of age may have immature pancreatic exocrine function which could impair hydrolysis of RAVICTI leading to impaired absorption of phenylbutyrate and hyperammonemia. While the limited data available suggest that pancreatic enzymes present in newborns include pancreatic lipase-related protein and bile salt-stimulated lipase (Lindquist 2010), both of which hydrolyze RAVICTI in vitro (McGuire 2010), it is not known whether pancreatic function in newborns is sufficiently mature to digest RAVICTI. This is the first clinical study involving pediatric patients during the first 2 months of life.

Inclusion Criteria

 Male and female subjects up to 2 years of age
 Signed informed consent by subject’s parent/legal guardian
 UCD diagnosis or suspected diagnosis of any subtype, except N-acetyl glutamate synthetase deficiency. If UCD has not been previously confirmed by genetic testing, consent must be obtained from parent/legal guardian to perform genetic testing. Genetic testing for UCD diagnosis confirmation can occur after enrollment, but must be within 60 days of baseline. The results of the testing should be made available to parents/legal guardians per institutional practices, including the availability of genetic counseling. If genetic testing is inconsistent with or excludes a UCD diagnosis, the subject will be withdrawn from the study.
NOTE: UCD diagnosis is suspected when a subject experiences a hyperammonemic event with an ammonia level > 100 μmol/L and accompanied by signs and symptoms compatible with hyperammonemia in the absence of other obvious causes.

Exclusion Criteria

 Use of any investigational drug within 30 days of Day 1
 Uncontrolled infection (viral or bacterial) or any other condition known to precipitate hyperammonemic crises. Once these precipitating factors are medically controlled, patients presenting in crisis are eligible.
 Any clinical or laboratory abnormality of Grade 3 or greater severity according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03, except Grade 3 elevations in ammonia and liver enzymes, defined as levels 5–20 times ULN in ALT, AST, 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
 Known hypersensitivity to phenylacetate or phenylbutyrate
 Liver transplantation, including hepatocellular transplant
 Subjects on hemodialysis at time of initiating RAVICTI
 Subjects on RAVICTI for UCD management
 Currently treated with Carbaglu® (carglumic acid)