Clinical trial NCT03335488: Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders (UCDs)
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Urea Cycle Disorder
Keywords: Urea
Hyperammonemic crisis (HAC)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 16
Sex: ALL
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Controlled, Open-Label Parallel Arm study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of Treatment Success (Percentage of Participants Defined as Treatment Success at Week 4) During the Initial Treatment Period
timeFrame: Week 4
Secondary outcomes:
measure: Rate of Drug Discontinuations (Percentage of Participants Who Discontinued Study Drug) Due to Any Reason in the Initial Treatment Period
timeFrame: Baseline through Week 4
measure: Change From Baseline in Fasting Plasma Ammonia Levels During the Initial Treatment Period
timeFrame: Baseline, Initial Treatment Period Week 1, Week 2, Week 3, Week 4 (0, 4, 8 hours post dose)
measure: Plasma Ammonia Area Under the Curve (AUC) 0 to 8h at the End of the Initial Treatment Period
timeFrame: Week 4: hour 0 (predose), and hours 4 and 8 postdose
measure: Peak Plasma Concentration (Cmax) of Ammonia at the End of the Initial Treatment Period
timeFrame: Week 4: hour 0 (predose), and hours 4 and 8 postdose
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida (UF) - Shands Hospital
state: Florida
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas, Southwestern Medical Centre
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Padua
country: Italy
facility: Azienda Ospedaliera Universitaria Di Padova, U.O.C. Malattie Metaboliche Ereditarie, Dipartimento della Salute della Donna e del Bambino
state: Veneto
city: Rome
country: Italy
facility: Bambino Gesù Children's Research Hospital
city: Málaga
country: Spain
facility: Hospital Materno-Infantil (HRU Carlos Haya)
state: Andalucia
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Vizcaya
city: Bern
country: Switzerland
facility: Universitätsspital, Inselspital Bern
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: