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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 )
September 17, 2014
September 22, 2014
October 18, 2017
December 2014
October 17, 2016   (Final data collection date for primary outcome measure)
  • 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 ]
Successful transition to RAVICTI with controlled ammonia (i.e. no clinical symptoms and ammonia < 100 µmol/L) [ Time Frame: Up to 24 months ]
Complete list of historical versions of study NCT02246218 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
Not Provided
Not Provided
 
A Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate in Pediatric Subjects Under 2 Years of Age With Urea Cycle Disorders
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)

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.

Not Provided
Interventional
Phase 4
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Urea Cycle Disorder
Drug: RAVICTI
Other Names:
  • HPN-100
  • Glycerol Phenylbutyrate
  • GPB
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.
Intervention: Drug: RAVICTI
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
July 17, 2017
October 17, 2016   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
up to 2 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
 
 
NCT02246218
HPN-100-009
2016-003460-38 ( EudraCT Number )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics, LLC )
Horizon Therapeutics, LLC
Not Provided
Study Director: Colleen Canavan, BS Horizon Therapeutics, LLC
Horizon Pharma Ireland, Ltd., Dublin Ireland
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP