Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)
Condition: Urea Cycle Disorders
MeSH terms: Urea Cycle Disorders, Inborn
Intervention: HPN-100
Intervention description: HPN-100 is a pro-drug of PAA that combines with glutamine to provide an alternative vehicle for waste nitrogen elimination. It is a liquid with minimal taste and odor. Approximately three teaspoons of HPN-100 (~17.4 mL) delivers an equivalent amount as PBA that 40 tablets of NaPBA.
Intervention MeSH terms: Glycerol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 29 Days
Maximum age: 6 Years
Healthy volunteers: No
Keywords: Urea Cycle Disorder; UCD; GT4P; Buphenyl; hyperammonemia; sodium phenylbutyrate

Summary:

      This non-randomized, open-label study was approximately one year in duration and consisted of
      a short term NaPBA to HPN-100 switchover part involving two overnight stays followed by a
      12-month long term treatment period involving monthly visits.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects 29 days to < 6 years old. If the subject is born prematurely,
             calculation of the lower age limit begins at the corrected gestational age of 40
             weeks.

          -  Signed informed consent by the subject's legally acceptable representative

          -  Suspected or confirmed UCD diagnosis of any subtype, except NAGS deficiency

          -  On stable dose of NaPBA powder for at least 5 days before Day 1

          -  Not receiving sodium benzoate for at least 5 days before Day 1

          -  No concomitant illness which would preclude safe participation as judged by the
             investigator

          -  Able to receive medication orally

          -  Has not undergone liver transplantation, including hepatocellular transplantation

          -  Judged sufficiently stable and compliant with diet and treatment to be suitable for
             enrollment

        Exclusion Criteria:

          -  Screening ammonia level > 100 μmol/L and signs and symptoms indicative of
             hyperammonemia; subjects may be rescreened after their ammonia is controlled and they
             are clinically stable, at the discretion of the investigator

          -  Use of any investigational drug within 30 days of Day 1

          -  Active infection (viral or bacterial) or any other condition that may increase ammonia
             levels

          -  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 ULN (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 PAA or PBA

          -  Liver transplant, including hepatocellular transplant

          -  Currently treated with Carbaglu® (carglumic acid)