Conditions: Tetrahydrobiopterin Deficiencies Hyperphenylalaninemia, Non-Phenylketonuric
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 12
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the ability of Phenoptin to control blood phenylalanine levels in subjects who have hyperphenylalaninemia due to a primary BH4 deficiency and to evaluate the safety of Phenoptin in this population. Some subjects were receiving non-registered formulations of BH4 at enrollment and this treatment was suspended after Part 1 and within one day the subjects started Phenoptin at approximately the same dose.

Detailed description:
Within 4 weeks of completing screening assessments to determine eligibility, subjects will be enrolled in the study. The study will be conducted in two parts.

Part 1: After screening, all subjects will be followed for two weeks without modification of their baseline medical or dietary care.

Part 2: Beginning at Week 2, subjects who were receiving non-registered formulations of BH4 at enrollment will suspend this treatment and within one day will start Phenoptin at approximately the same dose of the non-registered BH4 formulation. Subjects not receiving BH4 at enrollment will begin treatment with Phenoptin at approximately 5 mg/kg/day, given orally, prior to meals.

At the discretion of the Investigator, the Phenoptin dose may be adjusted up or down at the Week 6 visit to control blood Phe levels (\<360 µmol/L), or to optimize the clinical effect. The maximum dose allowed will be approximately 20 mg/kg/day. All subjects will receive Phenoptin for a total of 8 weeks. Subjects will be instructed to continue their usual diet without modification. Study visits will occur every other week.

Tyrosine, biopterin and neopterin will be analyzed at the following visits: Week 0 (enrollment), Week 2 (prior to dosing with Phenoptin), Week 8 (after 6 weeks of treatment with Phenoptin) and Week 10 (after 8 weeks of treatment with Phenoptin).During each visit, blood Phe level will be measured (2.5-5 hours after a meal), and safety evaluations will be performed. Safety will be assessed by monitoring adverse events and vital signs, performing physical examinations, assessing signs and symptoms of primary BH4 deficiency (i.e., neurological symptoms such as seizures, changes in muscle tone, weakness, etc.) and clinical laboratory tests (chemistry, hematology and urinalysis).

Extension: Upon completion of 8 weeks of treatment (i.e., at the Week 10 visit), subjects will be offered the option to continue treatment with Phenoptin in an extension of this study. Participation in the study extension will continue until one of the following occurs:

1. the subject withdraws consent and discontinues from the study,
2. the subject is discontinued from the study at the discretion of the investigator,
3. the study drug is available through the appropriate marketing approval, or
4. the study is terminated.

During the extension period, study drug will be dispensed to subjects monthly, and study visits will be required every 3 months. The Phenoptin dose may be adjusted at any visit during the study extension at the discretion of the Investigator. The maximum dose allowed will be approximately 20 mg/kg/day.

Arms:
arm 1: 5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels

Outcomes were also evaluated by the subject's type of BH4 deficiency either defects in the genes encoding the enzymes involved in biosynthesis or defects in the genes encoding the enzymes involved in recycling.

Interventions: intervention 1: Phenoptin
Intervention descriptions: intervention 1: 5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels

Protocol document: