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A Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate in Pediatric Subjects Under 2 Years of Age With Urea Cycle Disorders

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02246218
First Posted: September 22, 2014
Last Update Posted: October 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics, LLC )
  Purpose

This is an open-label study consisting of a transition period to RAVICTI, followed by a safety extension period for at least 6 months and up to 24 months of treatment with RAVICTI, depending on age at enrollment. It is designed to capture information important for evaluating safety, pharmacokinetics and efficacy in young children.

Subjects who are followed by or referred to the Investigator for management of their UCD. Subjects eligible for this study will include patients ranging from newborn to < 2 years of age with either a diagnosed or clinically suspected UCD.


Condition Intervention Phase
Urea Cycle Disorder Drug: RAVICTI Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate (GPB; RAVICTI®) in Pediatric Subjects Under Two Years of Age With Urea Cycle Disorders (UCDs)

Resource links provided by NLM:


Further study details as provided by Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics, LLC ):

Primary Outcome Measures:
  • Successful transition to RAVICTI 2 month to 2 year with controlled ammonia (i.e. no clinical symptoms and ammonia < 100 µmol/L) [ Time Frame: Up to day 7 ]
  • Successful transition to RAVICTI birth to 2 months with controlled ammonia (i.e. no clinical symptoms and ammonia < 100 µmol/L) [ Time Frame: Up to day 7 ]

Secondary Outcome Measures:
  • Rate of hyperammonemic crises during the first 6 months on RAVICTI [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Rate of Adverse Events [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Amino Acid Assessment [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Assessment of Growth and Development- Body Mass Index (BMI) [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
    Body Mass Index will be calculated as weight divided by height squared. Measure of height and weight are taken at least once, up to twice during each scheduled study visit. Z-scores and percentiles (based on the most recent Centers for Disease Control and Prevention [CDC] growth charts) will be calculated.

  • Assessment of Growth and Development- Body Surface Area (BSA) [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
    Calculated using Mosteller Method. Measure of height and weight are taken at least once, up to twice during each scheduled study visit. Z-scores and percentiles (based on the most recent Centers for Disease Control and Prevention [CDC] growth charts) will be calculated.

  • Plasma phenylbutyrate/phenylbutyric acid (PBA) Cmax [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma phenylbutyrate/phenylbutyric acid (PBA) Cmin [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma phenylbutyrate/phenylbutyric acid (PBA) AUC(0-last) area under the concentration-time curve [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma phenylbutyrate/phenylbutyric acid (PBA) Tmax [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma Acidphenylacetate/phenylacetic acid (PAA) Cmax [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma Acidphenylacetate/phenylacetic acid (PAA) Cmin [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma Acidphenylacetate/phenylacetic acid (PAA) AUC(0-last) area under the concentration-time curve [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma Acidphenylacetate/phenylacetic acid (PAA) Tmax [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma phenylacetylglutamine (PAGN) Cmax [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma phenylacetylglutamine (PAGN) Cmin [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma phenylacetylglutamine (PAGN) AUC(0-last) area under the concentration-time curve [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Plasma phenylacetylglutamine (PAGN) Tmax [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
  • Assessment of Urinary Acidphenylacetate/phenylacetic acid (PAA) concentration [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
    Urinary PAA concentration will be measured through urine collection.

  • Assessment of Urinary Phenylacetylglutamine (PAGN) concentration [ Time Frame: Every month for the first 6 months and every 3 months thereafter up to 24 months ]
    Urinary PAGN concentration will be measured through urine collection.


Enrollment: 27
Study Start Date: December 2014
Study Completion Date: July 17, 2017
Primary Completion Date: October 17, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAVICTI
RAVICTI Oral Liquid should be administered just prior to breastfeeding or intake of formula or food. The recommended dosing regimen is 3-6 times per day depending on feeding schedule and at the discretion of the Investigator.
Drug: RAVICTI
Other Names:
  • HPN-100
  • Glycerol Phenylbutyrate
  • GPB

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 2 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects up to 2 years of age
  • Signed informed consent by subject's parent/legal guardian
  • UCD diagnosis or suspected diagnosis of any subtype, except N-acetyl glutamate synthetase deficiency. If UCD has not been previously confirmed by genetic testing, consent must be obtained from parent/legal guardian prior to perform genetic testing. If genetic testing is inconsistent with or excludes a UCD diagnosis, the subject will be withdrawn from the study.

Exclusion Criteria:

  • Use of any investigational drug within 30 days of Day 1
  • Uncontrolled infection (viral or bacterial) or any other condition known to precipitate hyperammonemic crises. Once these precipitating factors are medically controlled, patients presenting in crisis are eligible.
  • Any clinical or laboratory abnormality of Grade 3 or greater severity according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03, except Grade 3 elevations in ammonia and liver enzymes, defined as levels 5-20 times the upper limit of normal in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma glutamyl transpeptidase (GGT) in a clinically stable subject
  • Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the subject at increased risk by participating in this study
  • Known hypersensitivity to phenylacetate (PAA) or phenylbutyrate (PBA)
  • Liver transplantation, including hepatocellular transplant
  • Subjects on hemodialysis at time of initiating RAVICTI
  • Subjects on RAVICTI for UCD management
  • Currently treated with Carbaglu® (carglumic acid)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02246218


Locations
United States, California
Kaiser Permanente Regional Metabolic Center
Los Angeles, California, United States, 90027
Stanford Center for Clinical & Translational Research & Education
Palo Alto, California, United States, 94034
United States, District of Columbia
Children's National Medical Center
Washington, D.C., District of Columbia, United States, 20010
United States, Florida
Shands at University of Florida
Gainesville, Florida, United States, 32610
United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maine
Maine Medical Center
Portland, Maine, United States, 04102
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Canada
The Hospital for Sick Children
Toronto, Canada, M5G 1Hs
Sponsors and Collaborators
Horizon Therapeutics, LLC
Investigators
Study Director: Colleen Canavan, BS Horizon Therapeutics, LLC
  More Information

Additional Information:
Responsible Party: Horizon Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT02246218     History of Changes
Other Study ID Numbers: HPN-100-009
2016-003460-38 ( EudraCT Number )
First Submitted: September 17, 2014
First Posted: September 22, 2014
Last Update Posted: October 18, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics, LLC ):
Urea Cycle Disorder
UCD
Buphenyl
Glycerol Phenylbutyrate
Ravicti
Hyperammonemia
Sodium Phenylbutyrate
GPB
HPN-100

Additional relevant MeSH terms:
Disease
Urea Cycle Disorders, Inborn
Pathologic Processes
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Glycerol
4-phenylbutyric acid
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents