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

NCT01347073 | Completed Phase 3 Results DMC

• 1 other identifier: HPN-100-012
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 8

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.

Conditions

Urea Cycle Disorders

Keywords

Urea Cycle Disorder; UCD; GT4P; Buphenyl; hyperammonemia; sodium phenylbutyrate

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  Rate of adverse events during the Switch-Over portion of the Protocol

  2 weeks

• Adverse Events

  Rate of adverse events during the Safety Extension portion of the protocol ( please note: HPN-100 treatment only during Safety Extension )

  12 months

Secondary Outcomes (3)

• Blood Ammonia

  2 weeks

• Frequency of Ammonia Levels Greater Than the Upper Limit of Normal (ULN) on HPN-100 Compared With NaPBA

  2 weeks

• Hyperammonemic Crisis

  1 year

Study Arms (1)

HPN-100

EXPERIMENTAL

Switch over from sodium phenylbutyrate to open label HPN-100 oral liquid over 10 days then open label, long term treatment for 12 months

Drug: HPN-100

Interventions

HPN-100 DRUG

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.

Also known as: RAVICTI, Glycerol phenylbuterate

HPN-100

Eligibility Criteria

• Age: 29 Days - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amgen: lead

Study Sites (8)

UCLA Pediatrics/Genetics

Los Angeles, California, 90404, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Maine Medical Center

Portland, Maine, 04101, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Mokhtarani M, Diaz GA, Rhead W, Berry SA, Lichter-Konecki U, Feigenbaum A, Schulze A, Longo N, Bartley J, Berquist W, Gallagher R, Smith W, McCandless SE, Harding C, Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Dickinson K, Moors T, Norris C, Coakley D, Milikien DA, Nagamani SC, Lemons C, Lee B, Scharschmidt BF. Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio. Mol Genet Metab. 2013 Dec;110(4):446-53. doi: 10.1016/j.ymgme.2013.09.017. Epub 2013 Oct 8.

  PMID: 24144944 DERIVED

• Smith W, Diaz GA, Lichter-Konecki U, Berry SA, Harding CO, McCandless SE, LeMons C, Mauney J, Dickinson K, Coakley DF, Moors T, Mokhtarani M, Scharschmidt BF, Lee B. Ammonia control in children ages 2 months through 5 years with urea cycle disorders: comparison of sodium phenylbutyrate and glycerol phenylbutyrate. J Pediatr. 2013 Jun;162(6):1228-34, 1234.e1. doi: 10.1016/j.jpeds.2012.11.084. Epub 2013 Jan 13.

  PMID: 23324524 DERIVED

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn; Hyperammonemia

Interventions

glycerol phenylbutyrate

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The protocol was designed to capture information important for evaluating safety, pharmacokinetics, and efficacy while recognizing sampling limitations in young children and current standard of care.

Results Point of Contact

• Title: Craig James R.N. Associate Dir. UCD Clinical Operations
• Organization: Hyperion Therapeutics, Inc.

craig.james@hyperiontx.com

(650) 745- 7480

Study Officials

• F MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2011
• First Posted: May 4, 2011
• Study Start: July 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: March 1, 2013
• Last Updated: July 11, 2024
• Results First Posted: May 28, 2015

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (8)