Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)

This study has been completed.
Information provided by (Responsible Party):
Hyperion Therapeutics, Inc. Identifier:
First received: April 29, 2011
Last updated: April 3, 2013
Last verified: April 2013

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.

Condition Intervention Phase
Urea Cycle Disorders
Drug: HPN-100
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Switch-Over, Open-Label Study of the Safety, Pharmacokinetics, and Efficacy of HPN-100, Followed by Long-Term Treatment With HPN-100, in Pediatric Subjects Under 6 Years of Age With Urea Cycle Disorders (UCDs)

Resource links provided by NLM:

Further study details as provided by Hyperion Therapeutics, Inc.:

Primary Outcome Measures:
  • Rate of adverse events. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Comparison of ammonia control, assessed as 24 hr area under the curve, on NaPBA and HPN-100 (switchover only) [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Comparative pharmacokinetics of NaPBA and HPN-100 (switchover only) [ Time Frame: 24 hour ] [ Designated as safety issue: No ]
    Multiple plasma and urine samples will be collected to measure PAA (phenylacetate), PBA (phenylbutyrate / phenylbutyric acid), and PAGN (phenylacetylglutamine).

  • Frequency of hyperammonemic crises as compared with prior to enrollment (extension phase) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: July 2011
Study Completion Date: March 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HPN-100 Drug: HPN-100
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.

Detailed Description:

This was an open-label study consisting of a 10-day switch-over period during which subjects were switched from their prescribed dose of sodium phenylbutyrate (BUPHENYLTM or NaPBA) to a dose of HPN-100 that delivered the same amount of the active ingredient, PBA, followed by long-term treatment with HPN-100 for up to 12 months. The study was designed to capture information important for evaluating safety, Pharmacokinetics, and efficacy while recognizing sampling limitations in young children and current standard of care. Patients eligible for this study included pediatric patients from 29 days to < 6 years of age with either a diagnosed or clinically suspected Urea Cycle Disorders (UCD) who are receiving a stable dose of the powder formulation of NaPBA. Subjects were clinically stable and had been receiving a stable dose NaPBA powder for at least 5 days at the time of enrollment.

During the switch-over part of the study, subjects switched from NaPBA to HPN-100 in one step and had two overnight stays with 24 hour blood sampling, the first of which was on Day 1, while still taking NaPBA, and the second of which was on approximately Day 10 while taking HPN-100. Subjects then continued in the long-term treatment phase which was 12 months in duration.


Ages Eligible for Study:   up to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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)
  Contacts and Locations
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Please refer to this study by its identifier: NCT01347073

United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States
United States, Maine
Maine Medical Center
Portland, Maine, United States
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States
United States, New York
Mount Sinai School of Medicine
New York, New York, United States
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States
United States, Texas
Baylor College of Medicine
Houston, Texas, United States
Sponsors and Collaborators
Hyperion Therapeutics, Inc.
  More Information

No publications provided by Hyperion Therapeutics, Inc.

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Hyperion Therapeutics, Inc. Identifier: NCT01347073     History of Changes
Other Study ID Numbers: HPN-100-012
Study First Received: April 29, 2011
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hyperion Therapeutics, Inc.:
Urea Cycle Disorder
sodium phenylbutyrate

Additional relevant MeSH terms:
Urea Cycle Disorders, Inborn
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases processed this record on May 21, 2015