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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01347073
Recruitment Status : Completed
First Posted : May 4, 2011
Results First Posted : May 28, 2015
Last Update Posted : January 16, 2017
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland

Tracking Information
First Submitted Date  ICMJE April 29, 2011
First Posted Date  ICMJE May 4, 2011
Results First Submitted Date  ICMJE April 3, 2015
Results First Posted Date  ICMJE May 28, 2015
Last Update Posted Date January 16, 2017
Study Start Date  ICMJE July 2011
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2015)
  • Adverse Events [ Time Frame: 2 weeks ]
    Rate of adverse events during the Switch-Over portion of the Protocol
  • Adverse Events [ Time Frame: 12 months ]
    Rate of adverse events during the Safety Extension portion of the protocol ( please note: HPN-100 treatment only during Safety Extension )
Original Primary Outcome Measures  ICMJE
 (submitted: May 3, 2011)
Rate of adverse events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2015)
  • Blood Ammonia [ Time Frame: 2 weeks ]
    24-hour ammonia AUC of blood ammonia levels on Days 1 (NaPBA) and 10 (HPN-100) were compared. Ammonia was assessed at Hour 0 (pre-first dose, fasted), Hour 8 (~2-4 hours after lunch or the second main meal and dose of NaPBA), Hour 12 (~4 hours after the last main meal) and 24 hours post-first dose (pre-first dose on following day, fasted).
  • Frequency of Ammonia Levels Greater Than the Upper Limit of Normal (ULN) on HPN-100 Compared With NaPBA [ Time Frame: 2 weeks ]
    Ammonia values were converted to SI units (umol/L) and normalized to a standard ULN of 35 umol/L prior to analysis
  • Hyperammonemic Crisis [ Time Frame: 1 year ]
    Rate of HAC during pre-enrollment on NaPBA compared to HAC during HPN-100 treatment
Original Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2011)
  • Comparison of ammonia control, assessed as 24 hr area under the curve, on NaPBA and HPN-100 (switchover only)
  • Comparative pharmacokinetics of NaPBA and HPN-100 (switchover only) [ Time Frame: 24 hour ]
    Muliple plasma and urine samples will be collected to measure PAA, PBA, and PAGN.
  • Frequency of hyperammonemic crises as compared with prior to enrollment (extension phase only)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)
Official Title  ICMJE 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)
Brief 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urea Cycle Disorders
Intervention  ICMJE 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.
Other Names:
  • Glycerol phenylbuterate
Study Arms  ICMJE Experimental: HPN-100
Switch over from sodium phenylbutyrate to open label HPN-100 oral liquid over 10 days then open label, long term treatment for 12 months
Intervention: Drug: HPN-100
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2013)
Original Estimated Enrollment  ICMJE
 (submitted: May 3, 2011)
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01347073
Other Study ID Numbers  ICMJE HPN-100-012
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Horizon Pharma Ireland, Ltd., Dublin Ireland
Study Sponsor  ICMJE Horizon Pharma Ireland, Ltd., Dublin Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Bruce F Scharschmidt, M.D. Hyperion Therapeutics
PRS Account Horizon Pharma Ireland, Ltd., Dublin Ireland
Verification Date June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP