To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs)
Long Term Use of HPN-100 in Urea Cycle Disorders
1 other identifier
interventional
88
2 countries
16
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started Oct 2010
Longer than P75 for phase_4
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 4, 2010
CompletedFirst Submitted
Initial submission to the registry
December 2, 2010
CompletedFirst Posted
Study publicly available on registry
December 10, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 16, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
February 16, 2017
CompletedResults Posted
Study results publicly available
May 4, 2018
CompletedAugust 22, 2024
July 1, 2024
6.4 years
December 2, 2010
February 16, 2018
July 30, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With at Least One Adverse Event
Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs). An AE/adverse experience was any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. For additional information regarding adverse events, please see the safety section of the record.
From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Secondary Outcomes (8)
Mean Normalized Blood Ammonia Levels
From baseline through the end of the study, up to 66 months
Number of Hyperammonemic Crises
From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Causes of Hyperammonemic Crises
From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)
Mean Child Behavior Checklist (CBCL) Problems Scores
Baseline, Month 12, Month 24, and study exit visit (up to 66 months)
- +3 more secondary outcomes
Study Arms (1)
HPN-100
EXPERIMENTALParticipants continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Interventions
Participants received individualized doses of HPN-100 orally, three times daily (TID) with meals. The initial dose was the same dose administered at the end of the HPN-100-005SE, HPN-100-007, or HPN-100-012SE studies. Dose adjustments (including frequency adjustments) were permitted as judged clinically appropriate by the investigator based on assessment of ammonia-scavenging needs (e.g., severity of the UCD defect, dietary protein intake, and urinary phenylacetylglutamine \[PAGN\] excretion). The maximum recommended dose of HPN-100 in participants weighing less than 20 kg was 0.53 mL/kg/day (equivalent to 600 mg/kg/day of NaPBA), and was 11.48 mL/m²/day in heavier subjects (equivalent to 13g/m²/day of NaPBA). The maximum HPN-100 dose recommended per protocol was 17.4 mL/day, which is equivalent to 20 g/day of NaPBA.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (16)
UCLA Pediatrics/Genetics
Los Angeles, California, 90095, United States
Stanford University School of Medicine
Palo Alto, California, 94305, United States
Denver Children's Hospital
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Maine Medical Center
Portland, Maine, 04102, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, 55454, United States
Mount Sinai School of Medicine
New York, New York, 10029, United States
University Hospitals Case Medical Center
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Children's Hospital of Pittsburg of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
University of Utah
Salt Lake City, Utah, 84112, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Colleen Canavan, Director
- Organization
- Horizon Therapeutics, LLC
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 2, 2010
First Posted
December 10, 2010
Study Start
October 4, 2010
Primary Completion
February 16, 2017
Study Completion
February 16, 2017
Last Updated
August 22, 2024
Results First Posted
May 4, 2018
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
- Access Criteria
- Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.