Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders (UCDs)
Condition: Urea Cycle Disorder
MeSH terms: Urea Cycle Disorders, Inborn
Intervention: RAVICTI; NaPBA
Intervention description: 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
Intervention MeSH terms: 4-phenylbutyric acid; Glycerol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, Controlled, Open-Label Parallel Arm study
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Urea; Hyperammonemic crisis (HAC)

Summary:

      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.
    

Eligibility 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 n-acetylglutamate synthetase (NAGS) deficiency.

          -  Suspected diagnosis is defined as having experienced a hyperammonemic crisis (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

               -  Birth 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.
                  Acceptable forms of contraception are (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 consecutive 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 sodium benzoate (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 phenylbutyric acid (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.