Urea Cycle Disorders (UCDs) MedDRA version: 20.0 Level: LLT Classification code 10013373 Term: Disorders of urea cycle metabolism System Organ Class: 100000161833
Conditions
Sponsors
Horizon Therapeutics, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
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 an HAC or a documented high ammonia of =100 µmol/L - Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing • Requires nitrogen binding agents according to the judgment of the Investigator • = 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 duration of 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. Are the trial subjects under 18? yes Number of subjects for this age range: 23 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Subject has received chronic treatment with an oral phenylbutyrate (RAVICTI, NaPBA, Pheburane, or other) longer than 14 consecutive days within one year prior to enrollment - Temporary use of oral PBA 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 • Have 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety, tolerability, pharmacokinetics (PK) and ammonia control of RAVICTI and NaPBA in UCD subjects not currently treated with phenylacetic acid (also referred to as phenylacetate; PAA) prodrugs.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint of this study is the Rate of Treatment Success: Efficacy ;Timepoint(s) of evaluation of this end point: The efficacy endpoint will be evaluated during the Initial Treatment Period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Efficacy a) Initial Treatment Period Endpoints (RAVICTI vs NaPBA) • Drug discontinuation due to any reason b) Transition, Maintenance, and Safety Extension Periods (RAVICTI) • Control of plasma ammonia • Annualized rate of HAC 2) Safety and Tolerability • Assessment of AEs • Standard clinical laboratory tests • Amino acid panel • Rate of drug discontinuation due to AEs 3) Clinical Outcome Assessments • Rate of treatment success in the Initial Treatment Period • Subject preference for study drug (Arm 2 after exposure to both RAVICTI and NaPBA) • Palatability of study drug (Hedonic Scale) • Changes in CGI scales (Investigator) • Neuropsychological assessments: CBCL or ABCL or ASR • EQ-5D-5L health status quality of life assessment ; Timepoint(s) of evaluation of this end point: a) Initial Treatment Period (RAVICTI vs NaPBA) • Drug discontinuation due to any reason • Amino acid panel • Standard clinical laboratory tests • Assessment of AEs • Rate of Treatment Success • EQ-5D-5L health status quality of life assessment b) Transition, Maintenance, and Safety Extension Periods (RAVICTI) • Control of plasma ammonia • Annualized rate of HAC • Amino acid panel • Standard clinical laboratory tests • Neuropsychological assessments: CBCL or ABCL or ASR • EQ-5D-5L health status quality of life assessment • Subject preference for study drug (Arm 2 after exposure to both RAVICTI and NaPBA) • Assessment of AEs | — |
Countries
Austria, Belgium, Italy, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactDirector, Clinical Drug Development
Horizon Therapeutics, LLC
Outcome results
None listed