Primary Outcome Measures:
- Safety, as assessed by reported adverse events, serious adverse events, symptom survey, vital signs, 12-lead ECG, clinical laboratory measurements, urinalysis, and urine orotic acid. [ Time Frame: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Pharmacokinetics (plasma and urine PK parameters of study drugs and their metabolites) [ Time Frame: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation ] [ Designated as safety issue: No ]
- Pharmacodynamics (venous ammonia levels and their correlation with PK parameters) [ Time Frame: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation ] [ Designated as safety issue: No ]
- Exploratory efficacy, as measured by TNUAC and peak/trough venous ammonia levels, venous ammonia, glutamine and glutamate levels at each timepoint, urinary excretion of PAGN, intrapatient variability of venous ammonia levels [ Time Frame: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation ] [ Designated as safety issue: No ]
- Drug preference for HPN-100 or Buphenyl® (as assessed by global preference question) [ Time Frame: End of Study ] [ Designated as safety issue: No ]
- Convenience and comfort associated with drug treatment (as assessed by UCD Drug Evaluation Questionnaire) [ Time Frame: Questionnaire administered at each visit ] [ Designated as safety issue: No ]
- Study drug compliance and diet (as assessed by diary data/interview) [ Time Frame: Assessed at each visit, except follow-up visit ] [ Designated as safety issue: No ]
When protein is broken down in the body, nitrogen is formed. In healthy individuals, the body combines this nitrogen with other molecules to create a harmless substance called urea, which is excreted in the urine. Patients with Urea Cycle Disorders (UCD) are unable to create as much urea from nitrogen, and therefore, toxic levels of nitrogen can accumulate in the body, causing harm. To treat these patients, doctors usually have the patient consume less protein and supplement certain amino acids that may be lacking. A drug called Buphenyl® is sometimes prescribed as an adjunctive treatment for the chronic maintenance of UCD patients in order to keep ammonia levels down. Some issues with Buphenyl® include a high pill burden (up to 40 pills per day), bad taste and odor, and high sodium content. Like Buphenyl®, HPN-100 provides an alternate way for the body to dispose of nitrogen, other than through the urea cycle. Unlike Buphenyl®, HPN-100 is an odorless, tasteless, concentrated oil that does not contain large amounts of sodium.