Study of the Safety of HPN (Hyperion)-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)

NCT00947297 | Completed Phase 3 Results DMC

• 1 other identifier: HPN-100-007
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 22

Brief Summary

This was a long-term safety study HPN-100 in urea cycle disorder (UCD) subjects. Subjects were assessed regularly for safety and control of their venous ammonia. Hyperammonemic events were characterized with respect to contributing factors, such as intercurrent illness, diet, and noncompliance with medication.

Conditions

Urea Cycle Disorders

Keywords

Urea Cycle Disorder; UCD; hyperammonemia; Buphenyl; Sodium Phenylbutyrate

Outcome Measures

Primary Outcomes (1)

• Rate of Adverse Events (Number of Participants Who Experienced Any AE Considered Related to Study Drug)

  1 year

Secondary Outcomes (3)

• Number and Causes of Hyperammonemic Events

  1 year

• Blood Ammonia Levels

  1 Year

• Patient Satisfaction With HPN-100

  Month 1 post dose

Study Arms (1)

HPN-100

EXPERIMENTAL

Patients who were treated with HPN-100

Drug: HPN-100

Interventions

HPN-100 DRUG

HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. Three teaspoons of HPN-100 (\~17.4 mL) delivers equivalent of PBA that 40 tablets of NaPBA do.

Also known as: GT4P, Glyceryl tri-(4-phenylbutyrate)

HPN-100

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects who completed HPN-100-006:
• \*Additionally, approximately 20 UCD subjects ≥ 6 years of age may be enrolled who have not participated in HPN-100-006. These subjects may include those who did not qualify HPN-100-006 (e.g., subjects between the ages of 6-17 years, subjects with other UCD subtypes, or adult subjects who have not taken sodium phenylbutyrate (NaPBA) in the past 6 months, etc.). For adult subjects not receiving NaPBA in the past 6 months, subjects must, in the judgment of the investigator, be anticipated to benefit from the addition of a nitrogen-scavenging agent to their current treatment. Clinical evidence of potential benefit from introduction of an ammonia-scavenging agent might include a recent history (in the past year) of clinically overt hyperammonemia accompanied by a venous ammonia ≥ 100 μmol/L, a recent history (within the past year) of protein intolerance, or a history of abnormally high venous ammonia levels accompanied by symptoms (e.g., headache) that might reasonably be attributed to hyperammonemia.
• Signed informed consent by subject and/or subject's legally acceptable representative.
• Diagnosis of urea cycle disorder (enzyme or transporter deficiency) confirmed via enzymatic, biochemical, or genetic testing.
• Able to perform and comply with study activities, including blood draws.
• Negative pregnancy test for all females of childbearing potential.
• All females of childbearing potential and all sexually active males must agree to use an acceptable method of contraception throughout the study.

You may not qualify if:

• Screening venous ammonia level of ≥ 100 μmol/L or signs and symptoms indicative of hyperammonemia; subjects may be re-screened after their venous ammonia is controlled, at the discretion of the investigator.
• History of 4 or more hyperammonemic events as defined in Section 3.5.1 in the preceding 12 months.
• Active infection (viral or bacterial) or any other condition that may increase venous ammonia levels.
• 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.
• Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication known to increase venous ammonia levels (e.g., valproate), within the 24 hours prior to Day 1 and throughout the study.
• History of QTc (QT interval corrected) prolongation, or a QTc interval ≥ 450 msec or an increase of ≥ 60 msec during the previous HPN-100 study if applicable.
• Known hypersensitivity to PAA or PBA.
• Liver transplant, including hepatocellular transplant.
• Breastfeeding or lactating females.

Sponsors & Collaborators

• Amgen: lead

Study Sites (22)

Long Beach Memorial

Long Beach, California, 90806, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Children's National Medical Center

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

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Univeristy of Iowa

Iowa City, Iowa, 52242, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

SNBL-Clinical Pharmacology Center

Baltimore, Maryland, 21201, United States

Location

Tufts-New England Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55454, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

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

• Diaz GA, Krivitzky LS, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, Longo N, Berquist W, Berry SA, Gallagher R, Lichter-Konecki U, Bartholomew D, Harding CO, Cederbaum S, McCandless SE, Smith W, Vockley G, Bart SA, Korson MS, Kronn D, Zori R, Merritt JL 2nd, C S Nagamani S, Mauney J, Lemons C, Dickinson K, Moors TL, Coakley DF, Scharschmidt BF, Lee B. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013 Jun;57(6):2171-9. doi: 10.1002/hep.26058. Epub 2013 Jan 3.

  PMID: 22961727 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

Results Point of Contact

• Title: Craig James
• Organization: Hyperion Therapeutics

craig.james@hyperiontx.com

650-745 7840

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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: July 24, 2009
• First Posted: July 28, 2009
• Study Start: November 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: November 1, 2011
• Last Updated: July 10, 2024
• Results First Posted: August 15, 2013

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

CA (1); US (21)