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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hyperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00947297
First received: July 24, 2009
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Urea Cycle Disorders
Drug: HPN-100
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Open-Label Study of the Safety of HPN-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Rate of Adverse Events (Number of Participants Who Experienced Any AE Considered Related to Study Drug) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number and Causes of Hyperammonemic Events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Number of hyperammonemic crises per patient


Enrollment: 60
Study Start Date: November 2009
Study Completion Date: November 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HPN-100
Patients who were treated with HPN-100
Drug: 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.

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.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00947297

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Sponsors and Collaborators
Hyperion Therapeutics, Inc.
  More Information

No publications provided by Hyperion Therapeutics, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hyperion Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00947297     History of Changes
Other Study ID Numbers: HPN-100-007
Study First Received: July 24, 2009
Results First Received: April 30, 2013
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hyperion Therapeutics, Inc.:
Urea Cycle Disorder
UCD
GT4P
hyperammonemia
Buphenyl
Sodium Phenylbutyrate

Additional relevant MeSH terms:
Disease
Urea Cycle Disorders, Inborn
Pathologic Processes
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
Metabolic Diseases

ClinicalTrials.gov processed this record on September 22, 2014