A study to compare RAVICTI® against Sodium Phenylbutyrate (NaPBA) in the treatment of Urea Cycle Disorders (UCDs) in patients who have not received Phenylbutyrate treatment before.
- Conditions
- rea Cycle Disorders (UCDs)MedDRA version: 18.1Level: LLTClassification code 10013373Term: Disorders of urea cycle metabolismSystem Organ Class: 100000004861Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2015-000075-27-IT
- Lead Sponsor
- Horizon Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 16
• Signed informed consent given by the subject or the subject’s parent/legal guardian for those under 18 years of age
• Male and female subjects with a suspected or confirmed UCD diagnosis of any subtype, except NAGS deficiency
- Suspected diagnosis is defined as having experienced a HAC or a documented high ammonia of =100 µmol/L (see protocol Section 3.3 for HAC definition)
- Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing
• Requires nitrogen-binding agents according to the judgment of the Investigator
• 2 years of age and older
• >15 kg in body weight
• 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 duration of the study and for 30 days after the last dose of study drug.. Appropriate contraceptive methods include hormonal contraceptives (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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 23
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
• Subject has received chronic treatment with RAVICTIor NaPBA longer than 14 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
• Have undergone liver transplantation, including hepatocellular transplant
- Subjects on NaBz at Baseline will be excluded if they are viewed by the Investigator as being unable to undergo NaBz withdrawal with concomitant replacement by a PAA prodrug during Period 1
• Known hypersensitivity to 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety, tolerability, pharmacokinetics (PK) and ammonia control of RAVICTI and NaPBA in UCD subjects not currently treated with phenylacetic acid (also referred to as phenylacetate; PAA) prodrugs.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint of this study is the Rate of Treatment Success: Efficacy ;Timepoint(s) of evaluation of this end point: The efficacy endpoint will be evaluated during the Crossover Periods
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Crossover Period Endpoints (RAVICTI vs. NaPBA)<br>• Rate of adverse events (AEs)<br>• Drug discontinuation due to AEs<br>• Subject preference for study drug after completing Crossover Period 2 (Day14) <br>• Palatability of study drug (Hedonic Scale) <br><br>Safety Extension Period Endpoints<br>• Annualized rate of HAC<br>• Changes in clinical global impression (CGI) scales (Investigator and Patient) <br>• Rate of AEs <br>• Drug discontinuation due to AEs <br>• Neuropsychological assessments: Child Behavior Checklist (CBCL) or Adult Behavior Checklist (ABCL)/Adult Self-Report (ASR)<br>• EQ-5D-5L health status quality of life assessment<br><br>Safety and Tolerability Endpoints<br>• Assessment of AEs<br>• Standard clinical laboratory tests<br>• Amino acid panel<br>• Drug preference <br>• Rate of drug discontinuation due to AEs<br><br><br>;Timepoint(s) of evaluation of this end point: Crossover Period (RAVICTI vs. NaPBA)<br>Safety Extension Period