Study of the Safety of HPN (Hyperion)-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)
Condition: Urea Cycle Disorders
MeSH terms: Urea Cycle Disorders, Inborn
Intervention: HPN-100
Intervention description: HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. Three teaspoons of HPN-100 (~17.4 mL) delivers equivalent of PBA that 40 tablets of NaPBA do.
Intervention MeSH terms: 4-phenylbutyric acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: Urea Cycle Disorder; UCD; hyperammonemia; Buphenyl; Sodium Phenylbutyrate

Summary:

      This was a long-term safety study HPN-100 in urea cycle disorder (UCD) subjects. Subjects
      were assessed regularly for safety and control of their venous ammonia. Hyperammonemic events
      were characterized with respect to contributing factors, such as intercurrent illness, diet,
      and noncompliance with medication.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects who completed HPN-100-006:

             *Additionally, approximately 20 UCD subjects ≥ 6 years of age may be enrolled who have
             not participated in HPN-100-006. These subjects may include those who did not qualify
             HPN-100-006 (e.g., subjects between the ages of 6-17 years, subjects with other UCD
             subtypes, or adult subjects who have not taken sodium phenylbutyrate (NaPBA) in the
             past 6 months, etc.). For adult subjects not receiving NaPBA in the past 6 months,
             subjects must, in the judgment of the investigator, be anticipated to benefit from the
             addition of a nitrogen-scavenging agent to their current treatment. Clinical evidence
             of potential benefit from introduction of an ammonia-scavenging agent might include a
             recent history (in the past year) of clinically overt hyperammonemia accompanied by a
             venous ammonia ≥ 100 μmol/L, a recent history (within the past year) of protein
             intolerance, or a history of abnormally high venous ammonia levels accompanied by
             symptoms (e.g., headache) that might reasonably be attributed to hyperammonemia.

          -  Signed informed consent by subject and/or subject's legally acceptable representative.

          -  Diagnosis of urea cycle disorder (enzyme or transporter deficiency) confirmed via
             enzymatic, biochemical, or genetic testing.

          -  Able to perform and comply with study activities, including blood draws.

          -  Negative pregnancy test for all females of childbearing potential.

          -  All females of childbearing potential and all sexually active males must agree to use
             an acceptable method of contraception throughout the study.

        Exclusion Criteria:

          -  Screening venous ammonia level of ≥ 100 μmol/L or signs and symptoms indicative of
             hyperammonemia; subjects may be re-screened after their venous ammonia is controlled,
             at the discretion of the investigator.

          -  History of 4 or more hyperammonemic events as defined in Section 3.5.1 in the
             preceding 12 months.

          -  Active infection (viral or bacterial) or any other condition that may increase venous
             ammonia levels.

          -  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.

          -  Use of any medication known to significantly affect renal clearance (e.g., probenecid)
             or to increase protein catabolism (e.g., corticosteroids), or other medication known
             to increase venous ammonia levels (e.g., valproate), within the 24 hours prior to Day
             1 and throughout the study.

          -  History of QTc (QT interval corrected) prolongation, or a QTc interval ≥ 450 msec or
             an increase of ≥ 60 msec during the previous HPN-100 study if applicable.

          -  Known hypersensitivity to PAA or PBA.

          -  Liver transplant, including hepatocellular transplant.

          -  Breastfeeding or lactating females.