Clinical trial NCT01257737: To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs)
Official title: Long Term Use of HPN-100 in Urea Cycle Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Urea Cycle Disorders
Keywords: Urea Cycle Disorders
GT4P
HPN-100
Sodium Phenylbutyrate (NaPBA)
Glyceryl tri-(4-phenylbutyrate)
Phenylbutyrate
Hyperion
BUPHENYL
hyperammonemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-12-10
Enrollment: 88
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was an open-label, long-term safety study of HPN-100 (RAVICTI; glycerol phenylbutyrate) in participants with a urea cycle disorder (UCD) who completed the safety extensions of HPN-100-005 (NCT00947544; HPN-100-005SE), HPN-100-006 (NCT00947297; HPN-100-007), or HPN-100-012 (NCT01347073; HPN-100-012SE). The initial studies were 1- to 2-week crossover studies, and their associated safety extensions were 12-month, open-label studies. All participants who completed the initial studies were eligible to enroll in the associated safety extension studies, and new participants were also permitted to enroll directly into the safety extension studies.

Detailed description: The duration of treatment in this study was open-ended. Participants were to return for clinic visits as prescribed by the investigator, and were to be seen at a minimum of every 6 months. At each clinic visit, participants were queried about any adverse events (AEs) or hyperammonemic crises (HACs) that occurred since the last visit. Physical and neurological examinations were performed, and blood samples were collected for the analysis of ammonia, amino acid panels, and routine clinical laboratory safety tests. Participants underwent neuropsychological testing at baseline, every 12 months thereafter, and at the final study visit.

Study acquired from Horizon in 2024.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects who completed Studies HPN-100-005SE, HPN-100-007, or HPN-100-012SE
* Signed informed consent by participant and/or participant'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 have put the participant at increased risk when participating
* Known hypersensitivity to PAA (phenylacetate) or PBA (phenylbutyrate).
* Liver transplant, including hepatocellular transplant
* Pregnant, breastfeeding or lactating females

Primary outcomes:
measure: Number of Participants With at Least One Adverse Event
timeFrame: From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Secondary outcomes:
measure: Mean Normalized Blood Ammonia Levels
timeFrame: From baseline through the end of the study, up to 66 months
measure: Number of Hyperammonemic Crises
timeFrame: From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
measure: Causes of Hyperammonemic Crises
timeFrame: From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
measure: Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)
measure: Mean Child Behavior Checklist (CBCL) Problems Scores
timeFrame: Baseline, Month 12, Month 24, and study exit visit (up to 66 months)
measure: Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
timeFrame: Baseline, Month 12, Month 24, and study exit visit (up to 66 months)
measure: Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)
measure: Mean California Verbal Learning Test Scores: Short and Long Delay Free Recall, Short and Long Delay Cued Recall, CVLT-II-Learning Slope, and Total Word Recognition Discrimination
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Pediatrics/Genetics
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: Denver Children's Hospital
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburg of UPMC
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: