- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03335488
Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders (UCDs)
A Randomised, Controlled, Open-Label Parallel Arm Study of Safety, PK and Ammonia Control of RAVICTI® (Glycerol Phenylbutyrate) Oral Liquid and Sodium Phenylbutyrate in Phenylbutyrate Treatment Naïve Patients With Urea Cycle Disorders
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: HorizonTherapeutics
- Phone Number: 866-479-6742
- Email: clinicaltrials@horizontherapeutics.com
Study Locations
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Rome, Italy, 00165
- Bambino Gesù Children's Research Hospital
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Veneto
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Padua, Veneto, Italy, 35128
- Azienda Ospedaliera Universitaria Di Padova, U.O.C. Malattie Metaboliche Ereditarie, Dipartimento della Salute della Donna e del Bambino
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Andalucia
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Málaga, Andalucia, Spain, 29006
- Hospital Materno-Infantil (HRU Carlos Haya)
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Vizcaya
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Barakaldo, Vizcaya, Spain, 48903
- Hospital Universitario de Cruces
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Bern, Switzerland, 3010
- Universitätsspital, Inselspital Bern
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Florida
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Gainesville, Florida, United States, 32610-0214
- University of Florida (UF) - Shands Hospital
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New York
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New York, New York, United States, 10029
- Mount Sinai School of Medicine
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Ohio
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Cleveland, Ohio, United States, 44106-6005
- University Hospitals Case Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15224
- Children's Hospital of Pittsburgh of UPMC
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Texas
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Dallas, Texas, United States, 753908565
- University of Texas, Southwestern Medical Centre
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Utah
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Salt Lake City, Utah, United States, 84132
- University of Utah
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 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.
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RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose
Other Names:
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Active Comparator: 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. |
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Rate of Treatment Success (Percentage of Participants Defined as Treatment Success at Week 4) During the Initial Treatment Period
Time Frame: Week 4
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A participant was considered a Treatment Success for the assigned treatment arm if the participant had not experienced an unprovoked hyperammonemic crisis (HAC) (i.e., a HAC that cannot be attributed to one or more specific precipitating factors such as infection, intercurrent illness, diet noncompliance, treatment noncompliance, etc.) on the assigned treatment and had met at least 2 of the following 3 criteria:
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Week 4
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Rate of Drug Discontinuations (Percentage of Participants Who Discontinued Study Drug) Due to Any Reason in the Initial Treatment Period
Time Frame: Baseline through Week 4
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Baseline through Week 4
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Change From Baseline in Fasting Plasma Ammonia Levels During the Initial Treatment Period
Time Frame: Baseline, Initial Treatment Period Week 1, Week 2, Week 3, Week 4 (0, 4, 8 hours post dose)
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Baseline, Initial Treatment Period Week 1, Week 2, Week 3, Week 4 (0, 4, 8 hours post dose)
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Plasma Ammonia Area Under the Curve (AUC) 0 to 8h at the End of the Initial Treatment Period
Time Frame: Week 4: hour 0 (predose), and hours 4 and 8 postdose
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Week 4: hour 0 (predose), and hours 4 and 8 postdose
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Peak Plasma Concentration (Cmax) of Ammonia at the End of the Initial Treatment Period
Time Frame: Week 4: hour 0 (predose), and hours 4 and 8 postdose
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Week 4: hour 0 (predose), and hours 4 and 8 postdose
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Denise Coughlan, Horizon Therapeutics, LLC
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Amino Acid Metabolism, Inborn Errors
- Urea Cycle Disorders, Inborn
- Physiological Effects of Drugs
- Antineoplastic Agents
- Protective Agents
- Cryoprotective Agents
- Glycerol
- 4-phenylbutyric acid
Other Study ID Numbers
- HPN-100-021
- 2015-000075-27 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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