To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs) - Full Text View

Purpose

The present protocol is a treatment protocol to allow continued use of HPN-100 for the treatment of UCD subjects who complete 12 months of treatment in Study HPN-100-005, (NCT00947544), HPN-100-007, (NCT00947297), or HPN-100-012, (NCT01347073). Under this protocol, long-term safety will continue to be assessed.

Condition	Intervention	Phase
Urea Cycle Disorders	Drug: HPN-100	Phase 4


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Long Term Use of HPN-100 in Urea Cycle Disorders

Resource links provided by NLM:

Genetics Home Reference related topics: N-acetylglutamate synthase deficiency argininosuccinic aciduria citrullinemia ornithine translocase deficiency succinic semialdehyde dehydrogenase deficiency

Drug Information available for: Carbamide Carbamide peroxide Sodium phenylbutyrate Glycerol phenylbutyrate

Genetic and Rare Diseases Information Center resources: Urea Cycle Disorders Inborn Amino Acid Metabolism Disorder

U.S. FDA Resources

Further study details as provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:

Primary Outcome Measures:

Rate of Adverse Events [ Time Frame: Every six months for 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Venous ammonia levels [ Time Frame: Every six months for two years ] [ Designated as safety issue: Yes ]
Number of hyperammonemic crises [ Time Frame: Every six months for two years ] [ Designated as safety issue: Yes ]
Neuropsychological testing [ Time Frame: Every twelve months for two years ] [ Designated as safety issue: Yes ]
Wechsler Abbreviated Scale of Intelligence (WASI) The California Verbal Learning Test (CVLT) Digit Span The Child Behavior Checklist (CBCL) Behavior Rating Inventory of Executive Function® (BRIEF®)
Causes of hyperammonemic crises [ Time Frame: Every six month for two years ] [ Designated as safety issue: Yes ]


Enrollment:	88
Study Start Date:	October 2010
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HPN-100 Subjects will continue treatment with HPN-100 after having completed HPN-100 treatment in HPN-100-005, HPN-100-007, or HPN-100-012.	Drug: HPN-100 HPN-100 will be administered orally three times daily (TID) with meals. The maximum recommended dose of HPN-100 in subjects weighing less than 20 kg is 0.53 mL/kg/day (equivalent to 600 mg/kg/day of NaPBA), and is 11.48 mL/m2/day in heavier subjects (equivalent to 13g/m2/day of NaPBA). The maximum HPN-100 dose should be 17.4 mL/day, which is equivalent to 20 g/day of NaPBA. Other Name: GT4P, Glyceryl tri-(4-phenylbutyrate)

Arms

Assigned Interventions

Experimental: HPN-100

Subjects will continue treatment with HPN-100 after having completed HPN-100 treatment in HPN-100-005, HPN-100-007, or HPN-100-012.

Drug: HPN-100

HPN-100 will be administered orally three times daily (TID) with meals. The maximum recommended dose of HPN-100 in subjects weighing less than 20 kg is 0.53 mL/kg/day (equivalent to 600 mg/kg/day of NaPBA), and is 11.48 mL/m2/day in heavier subjects (equivalent to 13g/m2/day of NaPBA). The maximum HPN-100 dose should be 17.4 mL/day, which is equivalent to 20 g/day of NaPBA.

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

Detailed Description:

The present protocol will allow subjects continued use of HPN-100 following their treatment and study completion in Study HPN-100-005, HPN-100-007, or HPN-100-012. Subjects will be able to continue in this study until approval and commercial availability of HPN-100 in each country participating in this study. Subjects will be required to return to the clinic every 6 months in which physical exam, safety labs, dietary assessment and neuropsychological testing will occur. Subjects will be dispensed sufficient HPN-100 to last until the next clinic visit.

Eligibility


Ages Eligible for Study:	1 Year and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female subjects who completed HPN-100-005, HPN-100-007, or HPN-100-012
Signed informed consent by subject and/or subject's legally authorized representative
Negative pregnancy test for all females of childbearing potential

Exclusion Criteria:

Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at increased risk when participating
Known hypersensitivity to PAA or PBA
Liver transplant, including hepatocellular transplant
Pregnant, 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: NCT01257737

Locations


United States, California
UCLA Pediatrics/Genetics
Los Angeles, California, United States, 90095
Stanford University School of Medicine
Palo Alto, California, United States, 94305
United States, Colorado
Denver Children's Hospital
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Maine
Maine Medical Center
Portland, Maine, United States, 04102
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
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
Children's Hospital of Pittsburg of UPMC
Pittsburg, Pennsylvania, United States, 15224
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, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8

Sponsors and Collaborators

Horizon Therapeutics, LLC

Investigators


Study Chair:	Colleen Canavan, BS	Horizon Pharma

More Information


Responsible Party:	Horizon Therapeutics, LLC
ClinicalTrials.gov Identifier:	NCT01257737 History of Changes
Other Study ID Numbers:	HPN-100-011
Study First Received:	December 2, 2010
Last Updated:	September 12, 2016
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board Canada: Health Canada

Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:


Urea Cycle Disorders GT4P HPN-100 Sodium Phenylbutyrate Glyceryl tri-(4-phenylbutyrate)	Phenylbutyrate Hyperion Buphenyl hyperammonemia

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