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

NCT ID: NCT00947297

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2011-11-30

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.

Detailed Description

This was a one year long-term safety study of HPN-100 in 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.

Forty subjects with a diagnosis of UCD who completed Study HPN-100-006 were enrolled.

Twenty additional UCD subjects ≥ 6 years of age were enrolled. These subjects included those who did not qualify for HPN-100-006 [e.g., subjects between the ages of 6-17; 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. See the inclusion criteria for examples of clinical evidence of potential benefit.

Monthly assessments included safety laboratory tests, amino acid panel, vital signs, electrocardiogram (ECG) monitoring, venous ammonia, and blood and urine metabolites. Adverse events (AEs) and concomitant medications were recorded on an ongoing basis.

Study acquired from Horizon in 2024.

Conditions

Urea Cycle Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HPN-100

Patients who were treated with HPN-100

Group Type: EXPERIMENTAL

HPN-100

Intervention Type: 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.

Interventions

HPN-100

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.

Intervention Type: DRUG

Other Intervention Names

GT4P, Glyceryl tri-(4-phenylbutyrate)

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Long Beach Memorial

Long Beach, California, United States

UCLA

Los Angeles, California, United States

Stanford University

Stanford, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Yale School of Medicine

New Haven, Connecticut, United States

Children's National Medical Center

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

University of Florida

Gainesville, Florida, United States

Univeristy of Iowa

Iowa City, Iowa, United States

Maine Medical Center

Portland, Maine, United States

SNBL-Clinical Pharmacology Center

Baltimore, Maryland, United States

Tufts-New England Medical Center

Boston, Massachusetts, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Mount Sinai School of Medicine

New York, New York, United States

Westchester Medical Center

Valhalla, New York, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 24144944 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22961727 (View on PubMed)

Other Identifiers

HPN-100-007

Identifier Type: -

Identifier Source: org_study_id