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

June 29, 2017 updated by: Wellstat Therapeutics
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 15 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wellstat Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Michael K. Bamat, Ph.D., Wellstat Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 8, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 10, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 31, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 401.13.001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

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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