This is a randomized, controlled, open-label parallel arm study to assess the safety, tolerability, pharmacokinetics and ammonia control, of RAVICTI® as compared to Sodium phenylbutyrate (NaPBA) in urea cycle disorder subjects not currently or previously chronically treated with phenylacetic acid (phenylacetate; PAA) prodrugs. The study design will include: 1) Baseline Period; 2) Initial Treatment Period; 3) a RAVICTI only Transition Period 4) a RAVICTI only Maintenance Period; and 5) a RAVICTI only Safety Extension Period. The study will run for approximately 25 weeks.
Study acquired from Horizon in 2024.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose
* NaPBA in patients weighing \< 20 Kg - 600 mg/Kg, maximum total daily dose * NaPBA in patients weighing \> 20 Kg - 13 g/m2, maximum total daily dose
University of Florida (UF) - Shands Hospital
Gainesville, Florida, United States
Mount Sinai School of Medicine
New York, New York, United States
University Hospitals Case Medical Center
Cleveland, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
University of Texas, Southwestern Medical Centre
Dallas, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Azienda Ospedaliera Universitaria Di Padova, U.O.C. Malattie Metaboliche Ereditarie, Dipartimento della Salute della Donna e del Bambino
Padua, Veneto, Italy
Bambino Gesù Children's Research Hospital
Rome, Italy
Hospital Materno-Infantil (HRU Carlos Haya)
Málaga, Andalusia, Spain
Hospital Universitario de Cruces
Barakaldo, Vizcaya, Spain
...and 1 more locations
Rate of Treatment Success (Percentage of Participants Defined as Treatment Success at Week 4) During the Initial Treatment Period
A participant was considered a Treatment Success for the assigned treatment arm if the participant had not experienced an unprovoked hyperammonemic crisis (HAC) (i.e., a HAC that cannot be attributed to one or more specific precipitating factors such as infection, intercurrent illness, diet noncompliance, treatment noncompliance, etc.) on the assigned treatment and had met at least 2 of the following 3 criteria: * Had absolute values at the 3 time points (pre-dose, after dose at 4 hours and 8 hours) of plasma ammonia levels which do not exceed ULN at the Week 4(End of Initial Treatment Period visit) * Had normal (≤ ULN) glutamine levels at the Week 4 (End of Initial Treatment Period visit at the time point Zero Hour. * Had normal (≤ ULN) essential amino acids including branched chain amino acid levels (threonine, phenylalanine, methionine, lysine, leucine, isoleucine, histidine, valine) at the End of Initial Treatment Period visit at time point Zero Hour.
Time frame: Week 4
Rate of Drug Discontinuations (Percentage of Participants Who Discontinued Study Drug) Due to Any Reason in the Initial Treatment Period
Time frame: Baseline through Week 4
Change From Baseline in Fasting Plasma Ammonia Levels During the Initial Treatment Period
Time frame: Baseline, Initial Treatment Period Week 1, Week 2, Week 3, Week 4 (0, 4, 8 hours post dose)
Plasma Ammonia Area Under the Curve (AUC) 0 to 8h at the End of the Initial Treatment Period
Time frame: Week 4: hour 0 (predose), and hours 4 and 8 postdose
Peak Plasma Concentration (Cmax) of Ammonia at the End of the Initial Treatment Period
Time frame: Week 4: hour 0 (predose), and hours 4 and 8 postdose
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