- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02110147
Open-Label Study of Uridine Triacetate in Pediatric Patients With Hereditary Orotic Aciduria
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Data to be collected during the Main Study include demographic, baseline disease information and medical history including all prior disease-directed therapy. In addition, vital signs, laboratory values and adverse events information will be collected and recorded. Urine samples will be obtained and measured for orotic acid and orotidine levels. Systemic levels of uridine will be evaluated from plasma samples collected at set timepoints.
Upon successful completion of the Main Study and entry into the Treatment Extension, physical exams and vital signs will be performed every six (6) months. Additionally, plasma samples to measure systemic levels of uridine and urine samples to measure levels of orotic acid and orotidine will be collected every (6) six months.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Michigan
-
Detroit, Michigan, United States, 48201
- Children's Hospital of Michigan - Specialty Center Detroit
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15224
- Children's Hospital of Pittsburgh of UPMC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria (Main Study):
- Patients with diagnosed hereditary orotic aciduria
- Judged by the investigator to have the initiative and means to be compliant with the protocol
- Able to take oral medications
- Able to provide written informed consent (patient or legally authorized representative)
- Females of childbearing potential must have a negative pregnancy test at screening
- Females of childbearing potential or males with partners of childbearing potential are to use one of the following acceptable birth control methods:
- Surgically sterile or partner is surgically sterile
- Using adequate contraception (hormonal contraceptives, double barrier methods, or intra-uterine devices)
- Patients who claim to be sexually inactive agree to use an acceptable method of contraception should she or he become sexually active from 14 days prior to first dosing, throughout the study and for 14 days after the last dose administration
Exclusion Criteria (Main Study):
- Has a known allergy to uridine triacetate or any of its excipients
- Known to have ornithine transcarbamoylase deficiency
- Unable to have the initiative and means to be compliant with the protocol
- Unable to be compliant with taking oral medications
- Unable to provide written informed consent (patient or legally authorized representative)
- Female who is pregnant or lactating
Inclusion Criteria (Treatment Extension)
- Patient successfully completed the Main Study
Exclusion Criteria (Treatment Extension)
- Patient did not successfully complete the Main Study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Uridine Triacetate to Replace Uridine
Replacement therapy for oral uridine with oral administration of uridine triacetate in patients with hereditary orotic aciduria who have received (or would reasonably be expected to receive) clinical benefit from treatment with exogenous uridine.
The starting dose of uridine triacetate will be 60 mg/kg/day which may be escalated to 300 mg/kg/day of oral uridine triacetate.
The dose may be given once a day or as equally divided doses twice a day.
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patients With Stable Predetermined Principal Hematologic Parameters
Time Frame: Days 28 and 42
|
Hereditary orotic aciduria patients will be taking uridine triacetate as replacement therapy for uridine.
The primary outcome measure will be based on predetermined principal hematologic parameter(s) based on the patient's response(s) to oral uridine when dosing is switched from oral uridine to oral uridine triacetate.
The primary outcome measure in patients not previously receiving uridine replacement therapy will be improvement in the patient's principal affected hematologic parameter(s) on Days 28 and 42 compared to baseline (Day 0) of the Main Study.
|
Days 28 and 42
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patients With Stable or Improved Orotic Acid and Orotidine Levels
Time Frame: Days 28 and 42
|
Significantly elevated urine orotic acid levels are characteristic of patients with HOA.
Therefore, urinary orotic acid and orotidine levels were assessed in patients at baseline (on uridine or uridine naïve) and on Day 28 and Day 42 following the switch to uridine triacetate.
The table below shows the number of participants with stable or improved orotic acid and orotidine levels at Day 28 and Day 42 compared to baseline.
|
Days 28 and 42
|
Patients With Levels of Uridine in the Plasma Consistent With Expected Therapeutic Benefit
Time Frame: Days 1 and 28
|
HOA is principally a chronic uridine deficiency disorder.
The purpose of uridine triacetate administration is to provide an exogenous source of uridine.
Therefore, plasma uridine levels were assessed at various time points (prior to dosing, 30 min, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours) following uridine triacetate dosing to ensure levels of uridine consistent with previously observed symptomatic improvement from administration of uridine were achieved.
The table below shows the number of participants with uridine levels consistent with or exceeding previously observed symptomatic improvements.
|
Days 1 and 28
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Michael K. Bamat, Ph.D., Wellstat Therapeutics
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 (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 401.13.001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
Clinical Trials on Hereditary Orotic Aciduria
-
McGill University Health Centre/Research Institute...UnknownMethylmalonic Acidemia | Malonic AciduriaCanada
-
Emma Marie Caroline SlackUniversity Children's HospitalCompletedInborn Errors of Metabolism | Propionic Aciduria | Methylmalonic Aciduria | Urea Cycle DisorderSwitzerland
-
Bambino Gesù Hospital and Research InstituteCatholic University of the Sacred HeartCompletedGenetic Disease | Retinopathy | Methylmalonic Aciduria and Homocystinuria,Cblc TypeItaly
-
Oregon Health and Science UniversityTerminatedImmune System Diseases | Lipid Metabolism, Inborn Errors | Mevalonic Aciduria | Mevalonate Kinase Deficiency | Periodic Fever Syndromes, HereditaryUnited States
-
Pharvaris Netherlands B.V.CompletedHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsBulgaria, United States, Spain, Israel, Germany, Canada, Czechia, France, Hungary, Italy, Netherlands, Poland, United Kingdom
-
University of UtahUniversity of Witwatersrand, South AfricaCompletedHereditary Elliptocytosis (HE) | Hereditary Pyropoikilocytosis (HPP)United States
-
Pharvaris Netherlands B.V.Active, not recruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States, Poland, Germany, Austria, Bulgaria, Canada, Ireland, Italy, United Kingdom
-
University of Texas Southwestern Medical CenterRecruiting
-
Myriad Genetic Laboratories, Inc.Myriad Genetics, Inc.CompletedHereditary CancerUnited States
-
Pharvaris Netherlands B.V.RecruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States, Bulgaria, Czechia, Hungary, Spain, France, Germany, Poland, Canada, Israel
Clinical Trials on uridine triacetate
-
Wellstat TherapeuticsApproved for marketing
-
Repligen CorporationCompletedBipolar DepressionUnited States
-
VA Office of Research and DevelopmentActive, not recruitingSuicidal IdeationUnited States
-
University of UtahNational Institute of Mental Health (NIMH)Completed
-
Hospital Universitario Infanta LeonorCompletedChronic Kidney Disease Requiring Chronic DialysisSpain
-
National Center for Research Resources (NCRR)University of California, San DiegoCompleted
-
University of UtahThe Depressive and Bipolar Disorder Alternative Treatment FoundationCompletedBipolar Disorder | Bipolar Depression | Manic DepressionUnited States
-
Shaare Zedek Medical CenterUnknown
-
National Institute of Allergy and Infectious Diseases...Terminated
-
Merck Sharp & Dohme LLCCompleted