Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU

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.