Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: sapropterin dihydrochloride
Intervention description: A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food.
Intervention MeSH terms: Verapamil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 95.0
Sex: All
Maximum age: 6 Years
Healthy volunteers: No
Keywords: Phenylketonuria; PKU; Kuvan; Phenoptin; Biopten; Neurocognitive Function; Phenylalanine

Summary:

      This multicenter, open label study is designed to evaluate the safety of Kuvan® and its
      effect on neurocognitive function, blood Phe concentration, and growth in children with PKU
      who are 0-6 years old.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Established diagnosis of PKU with hyperphenylalaninemia (HPA) documented in the
             medical record by at least 2 blood Phe concentrations greater than or equal to 360
             micromole/L (6 mg/dL) taken at least 3 days apart

          -  Documented blood Phe control (defined by the standard used at each treatment center)
             prior to study enrollment, if applicable (eg, the subject is old enough for these data
             to be collected); blood Phe concentrations for subjects < 6 months old at Screening
             must be considered controlled and stable by the Investigator

          -  Willing to adhere to a prescribed Phe restricted diet in order to maintain blood Phe
             concentrations within the recommended ranges established at the subject's study site

          -  Age 0 to 6 years old, inclusive, at Screening

          -  Parent(s) or guardian(s) willing and able to provide written, signed informed consent
             after the nature of the study has been explained, and prior to any research-related
             procedures

          -  Parent(s) or guardian(s) willing and able to comply with all study procedures

          -  Female subjects of childbearing potential (as determined by the investigator) and
             sexually mature male subjects willing to use a medically accepted method of
             contraception throughout the study. Female subjects of childbearing potential willing
             to undergo periodic pregnancy tests during the course of the study

        Exclusion Criteria:

          -  Established diagnosis of primary tetrahydrobiopterin (BH4) deficiency

          -  Known hypersensitivity to Kuvan or its excipients

          -  History of organ transplantation

          -  Perceived to be unreliable or unavailable for study participation or to have parents
             or legal guardians who are perceived to be unreliable or unavailable

          -  Use of methotrexate or other medications that inhibit folate metabolism

          -  Serious neuropsychiatric illness (eg, major depression) not currently under medical
             control

          -  Use of Kuvan or any investigational agent within 30 days prior to Screening, or known
             requirement for any investigational agent prior to completion of all scheduled study
             assessments

          -  Concurrent disease or condition that would interfere with study participation or
             safety (eg, seizure disorder, oral steroid-dependent asthma or other condition
             requiring oral or parenteral corticosteroid administration, or insulin dependent
             diabetes)

          -  Any condition that, in the view of the Principal Investigator (PI), renders the
             subject at high risk for failure to comply with treatment or to complete the study

          -  Use of phosphodiesterase type 5 (PDE5) inhibitor.