Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders (UCDs)

NCT ID: NCT03335488

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-20
• Study Completion Date: 2022-12-20

Brief Summary

This is a randomized, controlled, open-label parallel arm study to assess the safety, tolerability, pharmacokinetics and ammonia control, of RAVICTI® as compared to Sodium phenylbutyrate (NaPBA) in urea cycle disorder subjects not currently or previously chronically treated with phenylacetic acid (phenylacetate; PAA) prodrugs. The study design will include: 1) Baseline Period; 2) Initial Treatment Period; 3) a RAVICTI only Transition Period 4) a RAVICTI only Maintenance Period; and 5) a RAVICTI only Safety Extension Period. The study will run for approximately 25 weeks.

Detailed Description

Study acquired from Horizon in 2024.

Conditions

Urea Cycle Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAVICTI -> RAVICTI

Initial Treatment, Maintenance, Safety Extension Periods: RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose. Dosing will be based on participants disease and treatment status at entry to the study.

Group Type: EXPERIMENTAL

RAVICTI

Intervention Type: DRUG

RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose

NaPBA -> RAVICTI

Initial Treatment Period: NaPBA dosing based on participants disease and treatment status at entry to the study.

Transition, Maintenance, Safety Extension Periods: RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose. Dosing will be based on participants disease and treatment status at entry to the study.

Group Type: ACTIVE_COMPARATOR

NaPBA

Intervention Type: DRUG

• NaPBA in patients weighing < 20 Kg - 600 mg/Kg, maximum total daily dose
• NaPBA in patients weighing > 20 Kg - 13 g/m2, maximum total daily dose

Interventions

RAVICTI

RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose

Intervention Type: DRUG

NaPBA

• NaPBA in patients weighing < 20 Kg - 600 mg/Kg, maximum total daily dose
• NaPBA in patients weighing > 20 Kg - 13 g/m2, maximum total daily dose

Intervention Type: DRUG

Other Intervention Names

Glycerol phenylbutyrate; GPB; HPN-100; Sodium phenylbutyrate

Eligibility Criteria

Inclusion Criteria

• Signed informed consent given by the subject or the subject's parent/legal guardian for those under 18 years of age or the age of consent by local regulation.
• Male and female subjects with a suspected or confirmed UCD diagnosis of any subtype, except n-acetylglutamate synthetase (NAGS) deficiency.
• Suspected diagnosis is defined as having experienced a hyperammonemic crisis (HAC) or a documented high ammonia of >=100 µmol/L
• Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing.

• Requires nitrogen-binding agents according to the judgment of the Investigator
• Birth and older.
• All females of childbearing potential and all sexually active males must agree to use an acceptable method of contraception from signing the informed consent throughout the study and for 30 days after the last dose of study drug. Acceptable forms of contraception are (oral, injected, implanted or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active.

Exclusion Criteria

• Subject has received chronic treatment with an oral phenylbutyrate (RAVICTI, NaPBA, Pheburane, or other) longer than 14 consecutive days within one year prior to enrollment.
• Temporary use of NaPBA for acute management of a hyperammonemic crisis in the past is acceptable.

• Any concomitant illness (e.g., malabsorption or clinically significant liver or bowel disease) which would preclude the subject's safe participation, as judged by the Investigator.
• Has undergone liver transplantation, including hepatocellular transplant.
• Subjects on sodium benzoate (NaBz) at Baseline will be excluded if they are viewed by the Investigator as being unable to undergo NaBz transition to a PAA prodrug during the Initial Treatment Period.
• Known hypersensitivity to phenylbutyric acid (PBA) or any excipients of the NaPBA/PBA formulations.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed at the Baseline Visit prior to the start of study drug.

• Maximum Eligible Age: 99 Years
• 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

University of Florida (UF) - Shands Hospital

Gainesville, Florida, United States

Mount Sinai School of Medicine

New York, New York, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

University of Texas, Southwestern Medical Centre

Dallas, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Azienda Ospedaliera Universitaria Di Padova, U.O.C. Malattie Metaboliche Ereditarie, Dipartimento della Salute della Donna e del Bambino

Padua, Veneto, Italy

Bambino Gesù Children's Research Hospital

Rome, , Italy

Hospital Materno-Infantil (HRU Carlos Haya)

Málaga, Andalusia, Spain

Hospital Universitario de Cruces

Barakaldo, Vizcaya, Spain

Universitätsspital, Inselspital Bern

Bern, , Switzerland

Countries

United States; Italy; Spain; Switzerland

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000075-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HPN-100-021

Identifier Type: -

Identifier Source: org_study_id