Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children 6-17 Years of Age With Urea Cycle Disorders, With a Long-Term Safety Extension
Protocol HPN-100-005 is the first study of HPN-100 in pediatric subjects with urea cycle disorders (UCDs) and is a fixed-sequence, open-label, switch Over study of HPN-100 with a long-term (12 month) safety extension designed to assess the safety of HPN-100 and to prospectively assess its ability to control blood ammonia as compared with Sodium Phenylbutyrate (NaPBA). Upon DSMB review of the first ten subjects who complete the Switch Over part of the study, and with DSMB approval, up to an additional 20 subjects will be enrolled into the Safety Extension Part of the study. 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 (~17.4mL) delivers equivalent amount of PBA that 40 tablets of NaPBA do.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2, Fixed-Sequence, Open-Label, Switch-Over Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children 6-17 Years of Age With Urea Cycle Disorders, With a Long-Term Safety Extension|
- Rate of adverse events. [ Time Frame: 1 week on each treatment for a total of 2 weeks. ]
|Study Start Date:||March 2010|
This is a fixed-sequence, open-label, Switch Over study of HPN-100 with a long-term (12 month) Safety Extension part designed to assess the safety of HPN 100 in pediatric subjects and to prospectively assess the ability of HPN 100 to control blood ammonia as compared with NaPBA.
For those subjects who participate in the Switch Over part, NaPBA will be dosed three times daily (TID) with meals during the first week and the same PBA mole-equivalent dose of HPN-100 during the second week. If there are safety concerns regarding a single-step transition from NaPBA to HPN-100, at the investigator's discretion, the transition may occur in 2 steps such that in the second week subjects may receive 50% of the PBA equivalent dose as NaPBA and 50% as HPN-100 before receiving 100% of the PBA equivalent dose as HPN-100 in the third week. Serial blood samples will be collected for PK and blood ammonia assessments after each drug has reached steady state, which is achieved approximately 4 days after initiation of 100% NaPBA or HPN-100 treatment.
The subjects who complete the Switch Over part of the study, and up to 20 additional subjects, will be offered the opportunity to continue in the study by entering the Safety Extension part of the study to continue receiving open-label HPN-100 for up to 12 months.
Subjects who prematurely terminate the study during the switch-over period after enrollment will have all the safety assessments, including safety labs and a single blood sample drawn for measurement of phenylbutyrate (PBA), the active metabolite phenylacetate (PAA), and the terminal metabolite phenylacetylglutamine (PAGN). Subjects who have enrolled in the extension period of the study, either directly or following the Switch Over part, but prematurely terminate the study prior to completing the extension period will have Month 12 procedures performed, or at a minimum have safety assessments including safety labs and ammonia drawn. The time of day at which the blood sample is drawn will be recorded as well as the time since the last dose of medication was taken.
Subjects will follow a stable diet throughout the study as prescribed by the investigator and dietary compliance will be recorded at each study visit for both the Switch Over part and Safety Extension part of the study.
|United States, California|
|Los Angeles, California, United States, 90095|
|United States, District of Columbia|
|The George Washington MC Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, New York|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States|
|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|
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G1X8|