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

• Sponsor: Wellstat Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02110147
• Collaborator: (none)
• Enrollment: 4
• Locations: 2
• Arm: 1
• Actual Duration (Months): 29.3
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Apr 1, 2014
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Sep 8, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Patients With Stable Predetermined Principal Hematologic Parameters [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Michigan - Specialty Center Detroit	Detroit	Michigan	United States	48201
2	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224

Sponsors and Collaborators

• Wellstat Therapeutics

Investigators

• Study Director: Michael K. Bamat, Ph.D., Wellstat Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wellstat Therapeutics
• ClinicalTrials.gov Identifier: NCT02110147
• Other Study ID Numbers: 401.13.001
• First Posted: Apr 10, 2014
• Last Update Posted: Jul 31, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Purine-Pyrimidine Metabolism, Inborn Errors

Study Results

Participant Flow

Arm/Group Title	Single Arm
Arm/Group Description	All patients were treated with uridine triacetate oral granules.
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Single Arm
Arm/Group Description	All patients were treated with uridine triacetate oral granules.
Overall Participants	4
Age (Count of Participants)
<=18 years	3 75%
Between 18 and 65 years	1 25%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 25%
Male	3 75%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Patients With Stable Predetermined Principal Hematologic Parameters
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uridine Triacetate
Arm/Group Description	All patients were treated with uridine triacetate oral granules.
Measure Participants	4
Count of Participants [Participants]	4 100%

2. Secondary Outcome

Title	Patients With Stable or Improved Orotic Acid and Orotidine Levels
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uridine Triacetate
Arm/Group Description	All patients were treated with uridine triacetate oral granules.
Measure Participants	4
Day 28	4 100%
Day 42	4 100%

3. Secondary Outcome

Title	Patients With Levels of Uridine in the Plasma Consistent With Expected Therapeutic Benefit
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uridine Triacetate
Arm/Group Description	All patients were treated with uridine triacetate oral granules.
Measure Participants	4
Day 1	4 100%
Day 28	4 100%

Adverse Events

Time Frame	Safety data collected for 24 months.
Arm/Group Title	Single Arm
Arm/Group Description	All patients were treated with uridine triacetate oral granules.
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.