A Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate in Pediatric Subjects Under 2 Years of Age With Urea Cycle Disorders (UCDs)
- Conditions
- MedDRA version: 19.0Level: LLTClassification code 10013373Term: Disorders of urea cycle metabolismSystem Organ Class: 100000004861Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2016-003460-38-Outside-EU/EEA
- Lead Sponsor
- Horizon Therapeutics, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 24
• 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 prior to perform genetic testing. If genetic testing is inconsistent with or excludes a UCD diagnosis, the subject will be withdrawn from the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
•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 the upper limit of normal in alanine aminotransferase (ALT), aspartate aminotransferase (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 (PAA) or phenylbutyrate (PBA)
•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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: This is an open-label study consisting of a transition period to RAVICTI, followed by a safety extension period for at least 6 months and up to<br>24 months of treatment with RAVICTI, depending on age at enrollment. It is designed to capture information important for evaluating safety, pharmacokinetics and efficacy in young children.<br><br>Subjects who are followed by or referred to the Investigator for management of their UCD or assessment of high blood ammonia may be eligible for this study. Subjects eligible for this study will include patients ranging from newborn to < 2 years of age with either a diagnosed or clinically suspected UCD.<br>;Secondary Objective: Rate of hyperammonemic crises during the study while on RAVICTI. Rate of adverse events.<br>;Primary end point(s): Successful transition to RAVICTI with controlled ammonia (i.e. no clinical symptoms and ammonia < 100 1-mol/L)<br><br>;Timepoint(s) of evaluation of this end point: Up to day 7
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Rate of hyperammonemic crises during the first 6 months on RAVICTI <br>Rate of Adverse Events<br>Amino Acid Assessment<br>Assessment of Growth and Development<br>Pharmacokinetics Parameters of Plasma PBA, PAA and PAGN<br>Urinary PAA and PAGN concentrations;Timepoint(s) of evaluation of this end point: Every month for the first 6 months and every 3 months thereafter up to 24 months