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

NCT ID: NCT01257737

Last Updated: 2024-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-04
• Study Completion Date: 2017-02-16

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.

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.

Conditions

Urea Cycle Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HPN-100

Participants continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.

Group Type: EXPERIMENTAL

HPN-100

Intervention Type: DRUG

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.

Interventions

HPN-100

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.

Intervention Type: DRUG

Other Intervention Names

GT4P, Glyceryl tri-(4-phenylbutyrate), RAVICTI

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

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

UCLA Pediatrics/Genetics

Los Angeles, California, United States

Stanford University School of Medicine

Palo Alto, California, United States

Denver Children's Hospital

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Maine Medical Center

Portland, Maine, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Mount Sinai School of Medicine

New York, New York, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Children's Hospital of Pittsburg of UPMC

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HPN-100-011

Identifier Type: -

Identifier Source: org_study_id