Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders
![]() |
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03335488 |
Recruitment Status :
Recruiting
First Posted : November 7, 2017
Last Update Posted : April 18, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Urea Cycle Disorder | Drug: RAVICTI Drug: NaPBA | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 18 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Randomized, Controlled, Open-Label Parallel Arm study |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | February 20, 2018 |
Estimated Primary Completion Date : | September 2022 |
Estimated Study Completion Date : | March 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Arm 1, RAVICTI
Used for Baseline, Treatment, Transition, Maintenance, and Safety. Dosing will be based on participants disease and treatment status at entry to the study. RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose.
|
Drug: RAVICTI
RAVICTI, Oral Liquid Product 17.5 mL maximum total daily dose
Other Names:
|
Active Comparator: Arm 2, NaPBA (sodium phenylbutyrate)
Used for Baseline and Treatment. Sodium Phenylbutyrate (NaPBA). Dosing will be based on participants disease and treatment status at entry to the study.
|
Drug: NaPBA
Other Name: Sodium phenylbutyrate |
- Rate of Treatment Success [ Time Frame: Week 4 ]
A subject will be considered a Treatment Success for the assigned treatment arm if the subject has 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 has met at least 2 of the following 3 criteria:
- Has absolute values at the 3 time points (pre-dose, after dose at 4 hours and 8 hours) of plasma ammonia levels which do not exceed ULN at the Week 4(End of Initial Treatment Period visit)
- Has normal (≤ ULN) glutamine levels at the Week 4 (End of Initial Treatment Period visit at the time point Zero Hour.
- Has normal (≤ ULN) essential amino acids including branched chain amino acid levels (threonine, phenylalanine, methionine, lysine, leucine, isoleucine, histidine, valine) at the End of Initial Treatment Period visit at time point Zero Hour.
- Annualized Rate of Hyperammonemic Crisis (HAC) [ Time Frame: Week 25 ]Hyperammonemic Crisis (HAC) will be captured throughout the study.
- Amino Acid Assessment [ Time Frame: Day 1, Week 1, 2, 3, 4, 5, 9, 13, 17, 21, 25 ]The amino acid panel will include ornithine, aspartic acid, serine, threonine, glutamic acid, asparagine, proline, glutamine, alanine, glycine, valine, citrulline, methionine, cystine, leucine, isoleucine, phenylalanine, tyrosine, lysine, arginine, taurine, phosphoserine, phosphoethanolamine, alpha-aminobutyric acid, 1-methylhistidine, histidine, 3-methylhistidine, and argininosuccinate.
- Rate of Drug Discontinuations Due to Any Reasons [ Time Frame: Baseline through Week 4 ]
- Rate of Drug Discontinuations Due to Adverse Events [ Time Frame: Baseline through Week 25 ]
- Palatability of Study Drug (Hedonic Scale) [ Time Frame: Week 4 , Week 5 (End of transition period for participant on NaPBA arm) ]The Hedonic scale is a validated scale developed to assess palatability of medications. Participants (or parents or caregivers) are asked to rate the palatability of RAVICTI (glycerol phenylbutyrate) Oral Liquid and NaPBA based on the participant's reactions. There are 5 smiley faces to choose from. Happy face = likes very much through sad face = dislikes very much.
- Clinical Global Impression (CGI) Scales Severity (Investigator Only) [ Time Frame: Baseline, Week 13 and 25 ]Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of rating, relative to clinician's past experience with patient's who have the same diagnosis. Rating scale is 1 = normal not ill to 7 = extremely ill.
- Clinical Global Impression (CGI) Scales Improvement (Investigator Only) [ Time Frame: Baseline, Week 13 and 25 ]The CGI improvement scale is a 7 point scale that shows improvement. This scale requires the investigator to assess how much of the participant's illness has improved or worsened relative to a Baseline state. 1= very much improved to 7= very much worse.
- Neuropsychological Checklists Child Behavior (CBCL) [ Time Frame: Baseline, Week 13 and 25 ]CBCL is a questionnaire by which parents rate a child's problem behaviors and competencies. The preschool checklist (CBCL/1.5 to 5) is intended for use with children aged 18 months to 5 years. The school-age version (CBCL/6-18) is for children aged 6 to 18 years. It is used as a diagnostic tool for a variety of behavioral and emotional problems.
- Neuropsychological Checklist Adult Behavior (ABCL) [ Time Frame: Baseline, Week 13 and 25 ]The ABCL is a questionnaire used to obtain information about the individual's adaptive functioning and problems. It is intended for use with adults aged 19 to 59 years. This is a diagnostic tool for a variety of behavioral and emotional problems. It is completed by an observer who knows the individual well.
- Neuropsychological Assessment Adult Self Report (ASR) [ Time Frame: Baseline, Week 13 and 25 ]Assessment adult self report (ASR) is a questionnaire used to obtain information about the individual's adaptive functioning and problems. It will be completed by those participants able to self-complete the form.
- EQ-5D-5L Health Status Quality of Life [ Time Frame: Baseline,Week 4, 13 and 25 ]The EQ-5D-5L provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care as well as in population health surveys. It is designed for self-completion by participants or caregivers of subjects aged ≥12 years. There are 5 values, mobility, self care, usual activities, pain/discomfort, anxiety/depression. The questionnaire includes 5 levels, no problems, slight problems, moderate problems, severe problems, and extreme problems which are used for assessment.
- Plasma Concentration of Phenylbutyric Acid (PBA) [ Time Frame: Week 4 ]Blood samples will be collected for the assessment of the plasma level of PBA and plasma concentration levels will be summarized using descriptive statistics.
- Plasma Concentration of Phenylacetic Acid (PAA) [ Time Frame: Week 4 ]Blood samples will be collected for the assessment of the plasma level of PAA and plasma concentration levels will be summarized using descriptive statistics.
- Plasma Concentration of Phenylacetylglutamine (PAGN) [ Time Frame: Week 4 ]Blood samples will be collected for the assessment of plasma level of PAGN and plasma concentration levels will be summarized using descriptive statistics.
- Urinary Excretion of Phenylacetylglutamine (PAGN) [ Time Frame: Week 4 ]Urine samples will be collected at hours 0 and 8 for the assessment of urinary excretion of PAGN.
- Rate of Adverse Events [ Time Frame: Baseline through Week 25 and 30 days post last dose for SAEs ]Treatment Emergent Adverse Events will be summarized by treatment received.
- Drug preference (NaPBA arm only) [ Time Frame: Week 5 ]Measures which drug is preferred. Participant is queried directly however for younger children, the parent or legal guardian can report on behalf of the child if more appropriate.
- Plasma Ammonia Level [ Time Frame: Day 1, Week 1, 2, 3, 4, 5, 9, 13, 17, 21, 25 ]Plasma ammonia will be analyzed on Day 1, Week 1, 2, 3, 4, 5, 9, 13, 17, 21, 25.

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 99 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 NAGS deficiency.
- Suspected diagnosis is defined as having experienced a 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 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 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.

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): NCT03335488
Contact: HorizonTherapeutics | 866-479-6742 | clinicaltrials@horizontherapeutics.com |
United States, Florida | |
University of Florida (UF) - Shands Hospital | Recruiting |
Gainesville, Florida, United States, 32610-0214 | |
Contact: Roberto Zori, MD 352-273-7763 zorirt@peds.ufl.edu | |
Principal Investigator: Roberto Zori, MD | |
United States, New York | |
Mount Sinai School of Medicine | Completed |
New York, New York, United States, 10029 | |
United States, Ohio | |
University Hospitals Case Medical Center | Recruiting |
Cleveland, Ohio, United States, 44106-6005 | |
Contact: Dr. Laura Konczal, MD 216-201-5225 Laura.Konczal@UHhospitals.org | |
Principal Investigator: Dr. Laura Konczal, MD | |
United States, Pennsylvania | |
Children's Hospital of Pittsburgh of UPMC | Recruiting |
Pittsburgh, Pennsylvania, United States, 15224 | |
Contact: Dr. Gerard Vockley, MD, PhD 412-692-7530 Jennifer.baker@chp.edu | |
Contact: Jennifer Baker 412-692-7530 Jennifer.baker@chp.edu | |
Principal Investigator: Dr. Gerard Vockley, MD, PhD | |
United States, Texas | |
University of Texas, Southwestern Medical Centre | Recruiting |
Dallas, Texas, United States, 753908565 | |
Contact: Markey McNutt, MD, PhD 214-648-1814 Markey.McNutt@UTSouthwestern.edu | |
Principal Investigator: Markey McNutt, MD, PhD | |
United States, Utah | |
University of Utah | Recruiting |
Salt Lake City, Utah, United States, 84132 | |
Contact: Dr. Nicola Longo, M.D., PhD. 801-587-3605 Nicola.Longo@hsc.utah.edu | |
Contact: Carrie Bailey 801 587 3605 Carrie.Bailey@hsc.utah.edu | |
Principal Investigator: Dr. Nicola Longo, M.D., PhD. | |
Belgium | |
Cliniques Universitaires Saint-Luc | Withdrawn |
Brussels, Belgium, 1200 | |
Italy | |
Azienda Ospedaliera Universitaria Di Padova, U.O.C. Malattie Metaboliche Ereditarie, Dipartimento della Salute della Donna e del Bambino | Recruiting |
Padua, Veneto, Italy, 35128 | |
Contact: Alberto Burlina, MD +39 049 821 3569 alberto.burlina@unipd.it | |
Principal Investigator: Alberto Burlina, MD | |
Bambino Gesù Children's Research Hospital | Recruiting |
Rome, Italy, 00165 | |
Contact: Diego Martinelli, MD, PhD +39 06/68592275 diego.martinelli@opbg.net | |
Principal Investigator: Dr. Diego Martinelli, MD, PhD | |
Spain | |
Hospital Materno-Infantil (HRU Carlos Haya) | Recruiting |
Málaga, Andalucia, Spain, 29006 | |
Contact: Dr. Javier Blasco-Alonso, MD 34 951 29 21 91 javierblascoalonso@yahoo.es | |
Contact: Almudena Frias 34 951 29 21 91 | |
Principal Investigator: Dr. Javier Blasco-Alonso | |
Hospital Clinico Universitario de Santiago | Withdrawn |
Santiago de Compostela, Galicia, Spain, 15706 | |
Hospital Universitario de Cruces | Completed |
Barakaldo, Vizcaya, Spain, 48903 | |
Switzerland | |
Universitätsspital, Inselspital Bern | Completed |
Bern, Switzerland, 3010 | |
University Children's Hospital | Withdrawn |
Zurich, Switzerland, 75, 8032 |
Study Director: | Colleen Canavan, BS | Horizon Therapeutics, LLC |
Responsible Party: | Horizon Therapeutics, LLC |
ClinicalTrials.gov Identifier: | NCT03335488 |
Other Study ID Numbers: |
HPN-100-021 2015-000075-27 ( EudraCT Number ) |
First Posted: | November 7, 2017 Key Record Dates |
Last Update Posted: | April 18, 2022 |
Last Verified: | April 2022 |
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 |
Urea Hyperammonemic crisis (HAC) |
Urea Cycle Disorders, Inborn 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 4-phenylbutyric acid Glycerol Cryoprotective Agents Protective Agents Physiological Effects of Drugs Antineoplastic Agents |