Phase 3 study of HPN-100 in Japanese patients with urea cycle disorder

JRCT ID: jRCT2071220110

Registered date:28/02/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Urea cycle disorder
• Date of first enrollment: 10/04/2023
• Target sample size: 15
• Study type: Interventional

Intervention(s)

- The switch-over part of the study will last 2 weeks during which subjects will be switched from sodium phenylbutyrate (NaPBA) to HPN100 (NaPBA for the first 7 days and HPN-100 for the next 7 days). The extension part is administered HPN-100 for 12 months.
- The dosage of NaPBA is determined depending on the patients based on previous therapeutic dose. The dosage of HPN-100 equivalent to the dosage of NaPBA will be calculated using the following formula:
- NaPBA tablets daily dose (g) x 0.86=HPN-100 daily dose (mL)
- NaPBA granules daily dose (g) x 0.81=HPN-100 daily dose (mL)
-Newly enrolled subjects in the extension part will start treatment with HPN-100 at a dosage of 4.5 mL/m2/day and the dosage will be adjusted according to blood ammonia levels, protein intake, and symptoms. The recommended dose range approved in the US and Europe is 4.5 to 11.2 mL/m2/day (5.3 to 12.4 g/m2/day).
- Blood ammonia levels will be measured according to the schedule of study assessments.

Outcome(s)

• Primary Outcome: The blood ammonia levels 24-hour area under the curve at the last day of NaPBA administration (Day 7) and the last day of HPN-100 administration (Day 14)

Secondary Outcome

- Maximum blood ammonia levels on the last day of NaPBA and HPN-100 administration
- Mean blood ammonia levels on the last day of NaPBA and HPN-100 administration
- During NaPBA and HPN-100 administration period, the number and percentage of patients whose ammonia levels exceeded the upper limit of reference (ULN)
- NaPBA and PK parameters of the main metabolites of HPN-100 (PAA, PBA and PAGN)
- Cumulative 24-hour urinary PAGN (U-PAGN0-24) excretion on the last day of NaPBA and HPN-100 administration
- The correlation between U-PAGN0-24 excretion and AUCNH3, 0-24
- Glutamine values on the last day of NaPBA and HPN-100 administration
- Adverse events

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Patients diagnosed with urea cycle disorder (UCD) by genetic testing, enzymatic testing, and/or biochemical testing.
- If participating in the switch-over part, patients being treated for UCD with NaPBA and who has not changed dosage and administration of NaPBA for at least one week prior to the start of study drug administration (Day 1).
- If newly participating in the extension part, NaPBA has not been administered for at least 30 days prior to the start of study drug administration (Month 0).
- Patients who are judged to be sufficiently capable of undergoing the tests and observations conducted in this study.

Exclude criteria

- Patients who have a blood ammonia level 100 micro mol/L (170 micro g/dL) or more at screening or has symptoms and/or signs of hyperammonemia within at least 2 weeks prior to the screening visit. If ammonia level is controlled and stable for at least 14 days, re-screening may be allowed at the discretion of the Investigator etc.
- Patients with active infections (viral and bacterial) or other diseases that may affect blood ammonia levels.
- Patients who have received sodium benzoate within 1 week prior to the start of study drug administration.
- Patients with history of hypersensitivity to phenylbutyrate and/or phenylacetic acid.
- Patients who have undergone liver transplantation (including hepatocellular transplantation)

Related Information

• Primary Sponsor: Hiroiku Furukawa