A Phase 3 interventional study of uridine triacetate in Hereditary Orotic Aciduria, sponsored by Wellstat Therapeutics. Completed at 2 sites in United States. Open to participants aged 6 Months to 19 Years. Per ClinicalTrials.gov, last updated 2017-07-31.
Sponsored by Wellstat Therapeutics · Phase 3, Interventional, and Treatment
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.
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.
Wellstat Therapeutics is the lead sponsor of 6 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria (Main Study):
Exclusion Criteria (Main Study):
Inclusion Criteria (Treatment Extension)
Exclusion Criteria (Treatment Extension)
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
Also known as: PN401 (Company Code Name), 2',3',5'-tri-O-acetyluridine
Patients With Stable Predetermined Principal Hematologic Parameters
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.
Time frame: Days 28 and 42
Patients With Stable or Improved Orotic Acid and Orotidine Levels
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.
Time frame: Days 28 and 42
Patients With Levels of Uridine in the Plasma Consistent With Expected Therapeutic Benefit
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.
Time frame: Days 1 and 28
| Milestone | Single Arm |
|---|---|
| Started | 4 |
| Completed | 4 |
| Not completed | 0 |
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.
| Participants | Uridine Triacetate |
|---|---|
| Patients With Stable Predetermined Principal Hematologic Parameters | 4 |
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.
| Participants | Uridine Triacetate |
|---|---|
| Day 28 | 4 |
| Day 42 | 4 |
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.
| Participants | Uridine Triacetate |
|---|---|
| Day 1 | 4 |
| Day 28 | 4 |
Collected over Safety data collected for 24 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single Arm | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) |
| Age, Categorical(Participants) | Single Arm |
|---|---|
| <=18 years | 3 |
| Between 18 and 65 years | 1 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Single Arm |
|---|---|
| Female | 1 |
| Male | 3 |
| Region of Enrollment(participants) | Single Arm |
|---|---|
| United States | 4 |
Plan to share: Yes
No publications or documents are linked to this record.
Ran from Apr 2014 to primary completion in Dec 2014, 8 months.
Results were first posted in Jun 2017, 2 years 6 months after primary completion.
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Studies of the drug tested here: Uridine triacetate
Oroticaciduria 1
Wellstat Therapeutics