Dose-Escalation Safety Study of HPN-100 to Treat Urea Cycle Disorders
Condition: Urea Cycle Disorders
MeSH terms: Urea Cycle Disorders, Inborn
Intervention: HPN-100; BUPHENYL®
Intervention description: Subjects will be taking prescribed dose of Buphenyl® TID (not to exceed 20g/day) at least two weeks prior to enrollment. Subjects will take prescribed dose of Buphenyl® TID for first week of study, and then switch over to HPN-100 TID during a dose-escalation phase. The dose of HPN-100 will be increased and the dose of Buphenyl® will be decreased each week by 50 mg/kg until entire daily dose of phenylbutyrate is HPN-100. Target HPN-100 dose will contain the same amount of phenylbutyrate as the subject's prescribed daily dose of Buphenyl®. Subject will take HPN-100 alone for one week and then switch back to previous dose of Buphenyl for the last week of the study.; BUPHENYL® (sodium phenylbutyrate) tablets and powder have been approved for marketing in the United States since 1996 as an adjunctive therapy in the long-term management of patients with UCDs involving deficiencies of CPS, OTC, or ASS.
Intervention MeSH terms: 4-phenylbutyric acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Buphenyl; Sodium Phenylbutyrate; Urea Cycle Disorder; UCD

Summary:

      The purpose of this study is to determine whether HPN-100 is safe and tolerable in subjects
      with Urea Cycle Disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients at least 18 years old

          -  Signed written informed consent by patient or patient's representative

          -  Diagnosis of urea cycle enzyme deficiency confirmed via enzymatic or genetic testing

          -  Currently treated with Buphenyl® TID for a minimum of 2 weeks prior to Visit 1

          -  Able to perform study activities (including the ability to collect all urine in the
             clinic, i.e., no patients in diapers)

          -  Negative pregnancy test for all females of childbearing potential. All females of
             childbearing potential must agree to use an acceptable method of contraception
             throughout the study

        Exclusion Criteria:

          -  Use of any investigational drug within 30 days of Buphenyl® Visit 1

          -  Active infection (viral or bacterial) or any other condition that may increase ammonia
             levels

          -  Laboratory values outside the normal range that are determined to be clinically
             significant by the investigator

          -  Any clinical or laboratory abnormality of Grade 3 or greater severity according to the
             Common Terminology Criteria for Adverse Events v3.0 (CTCAE) (or for conditions not
             covered by the CTCAE, a severe or life-threatening toxicity); except that Grade 3
             elevations in liver enzymes are allowed in an otherwise clinically stable patient

          -  Use of any medication known to significantly affect renal clearance (e.g., probenecid)
             or to increase protein catabolism (e.g., corticosteroids), or other medication (e.g.,
             valproate) known to increase ammonia levels, within the 24 hours prior to Visit 1

          -  Preexisting QTc interval prolongation (> 450 msec for males or > 460 msec for females)

          -  Other severe chronic medical conditions

          -  Known hypersensitivity to PAA, PBA, or benzoate

          -  Creatinine levels equal to or greater than 1.5 × ULN

          -  Liver transplant