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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier:
NCT00947297
First received: July 24, 2009
Last updated: June 8, 2015
Last verified: June 2015
  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: 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 Horizon Pharma Ireland, Ltd., Dublin Ireland:

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

  • Blood Ammonia Levels [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    Venous Ammonia levels over time

  • Patient Satisfaction With HPN-100 [ Time Frame: Month 1 post dose ] [ Designated as safety issue: No ]
    Drug preference will be noted at week 3


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.
Other Name: GT4P, Glyceryl tri-(4-phenylbutyrate)

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   (Child, Adult, Senior)
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 (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.
  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

  Hide Study Locations
Locations
United States, California
Long Beach Memorial
Long Beach, California, United States, 90806
UCLA
Los Angeles, California, United States, 90095
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale School of Medicine
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
University of Florida
Gainesville, Florida, United States, 32611
United States, Iowa
Univeristy of Iowa
Iowa City, Iowa, United States, 52242
United States, Maine
Maine Medical Center
Portland, Maine, United States, 04102
United States, Maryland
SNBL-Clinical Pharmacology Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Tufts-New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Minnesota
University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55454
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Westchester Medical Center
Valhalla, New York, United States, 10595
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15260
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada
Sponsors and Collaborators
Horizon Pharma Ireland, Ltd., Dublin Ireland
Investigators
Principal Investigator: Brendan Lee, MD Baylor College of Medicine
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
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: June 8, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:
Urea Cycle Disorder
UCD
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
4-phenylbutyric acid
Glycerol
Antineoplastic Agents
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 28, 2016