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Open-Label Study of Uridine Triacetate in Pediatric Patients With Hereditary Orotic Aciduria

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ClinicalTrials.gov Identifier: NCT02110147
Recruitment Status : Completed
First Posted : April 10, 2014
Results First Posted : June 28, 2017
Last Update Posted : July 31, 2017
Sponsor:
Information provided by (Responsible Party):
Wellstat Therapeutics

Brief Summary:
This protocol has two parts - the Main Study which is 42 days in length and the Treatment Extension which allows the patients who complete the Main Study to continue receiving treatment with uridine triacetate. The purpose of this study is to replace oral administration of 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. It is also to document the continued clinical benefit of exogenous uridine when patients are switched from oral administration of uridine to oral administration of uridine triacetate.

Condition or disease Intervention/treatment Phase
Hereditary Orotic Aciduria Drug: uridine triacetate Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label Study of Uridine Triacetate in Pediatric Patients With Hereditary Orotic Aciduria
Actual Study Start Date : April 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : September 8, 2016

Resource links provided by the National Library of Medicine


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.
Drug: uridine triacetate
Other Names:
  • PN401 (Company Code Name)
  • 2',3',5'-tri-O-acetyluridine




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



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Ages Eligible for Study:   6 Months to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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): NCT02110147


Locations
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United States, Michigan
Children's Hospital of Michigan - Specialty Center Detroit
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
Wellstat Therapeutics
Investigators
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Study Director: Michael K. Bamat, Ph.D. Wellstat Therapeutics
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Responsible Party: Wellstat Therapeutics
ClinicalTrials.gov Identifier: NCT02110147    
Other Study ID Numbers: 401.13.001
First Posted: April 10, 2014    Key Record Dates
Results First Posted: June 28, 2017
Last Update Posted: July 31, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Additional relevant MeSH terms:
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Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases