HPN-100-021

Principal Investigator: Nicola Longo
Keywords: Urea Cycle Disorders , UCD , Ravicti , HPN-100 Department: Pediatric Genetics
IRB Number: 00105142 Co Investigator:  
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Recruiting

Contact Information

Carrie Bailey
carrie.bailey@hsc.utah.edu
8015873605

Brief Summary

The 2013 United States (US) Food and Drug Administration (FDA) approval of RAVICTI for UCD was based on clinical studies that included crossover comparison of ammonia control in stable UCD patients during equivalent steady-state dosing of NaPBA or RAVICTI, followed by long-term RAVICTI dosing studies. However, most UCD patients enrolled in these studies were
already on a stable dose of NaPBA. This study is a FDA post-marketing requirement and is designed to assess the safety, efficacy, and tolerability of RAVICTI as compared to NaPBA in patients who have not been treated chronically and presently are not being treated with oral phenylbutyrates (PAA prodrugs).


This clinical study, HPN-100-021, is the first controlled and randomised study of RAVICTI in thirty UCD patients who have not been exposed chronically to phenylbutyrate derivatives.

 

Study Objectives: 

To assess the safety, tolerability, pharmacokinetics (PK) and ammonia control of RA VICTI as compared to NaPBA in UCD subjects not currently or previously chronically treated with phenylacetic acid (also referred to as phenylacetate; PAA) prodrugs.

Inclusion Criteria

-Signed informed consent given by the subject or the subject's parent/legal guardian for those under 18 years of age or the age of consent by local regulation
- Male and female subjects with a suspected or confirmed UCD diagnosis of any subtype, except NAGS deficiency
- Suspected diagnosis is defined as having experienced a HAC or a documented high ammonia of > or equal to 100 μmol/L  
- Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing
• Requires nitrogen-binding agents according to the judgment of the Investigator
• > or equal to 2 months of age and older
• All females of childbearing potential and all sexually active males must agree to use an acceptable method of contraception from signing the informed consent throughout the study and for 30 days after the last dose of study drug. Appropriate contraceptive methods include hormonal contraceptives ( oral, injected, implanted, or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active.

Exclusion Criteria

• Subject has received chronic treatment with an oral phenylbutyrate (RAVICTI, NaPBA, Pheburane, or other) longer than 14 days within one year prior to enrollment
- Temporary use of NaPBA for acute management of a hyperammonemic crisis in the past is acceptable.
• Any concomitant illness ( e.g., malabsorption or clinically significant liver or bowel disease) which would preclude the subject's safe participation, as judged by the Investigator

• Has undergone liver transplantation, including hepatocellular transplant
• Subjects on NaBz at Baseline will be excluded if they are viewed by the Investigator as being unable to undergo NaBz transition to a PAA prodrug during the Initial Treatment Period
• Known hypersensitivity to PBA or any excipients of the NaPBA/PBA formulations.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed at the Baseline Visit prior to the start of study drug.