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

Rigorous control of diet is typically advocated in children 4 years and under with PKU because brain sensitivity to high Phe concentrations is expected to be greatest during these years of rapid neurocognitive development. Prolonged high blood Phe concentrations are neurotoxic and lead to impairment of intelligence and other brain functions (such as attentiveness). Reduction of blood Phe concentrations through dietary control is an important determinant of long-term neurologic outcome in PKU patients, and reduction of blood Phe concentrations in patients with PKU has been shown to decrease the long term risk of neurologic injury. It is difficult for many patients to maintain reduced blood Phe, and many patients with PKU experience some degree of neurological impairment despite efforts to maintain dietary Phe control. The strongest determinant of intelligence quotient (IQ) and cognitive function is compliance with blood Phe control. Several clinical studies with Kuvan have already demonstrated efficacy in reducing blood Phe in subjects older than 4 years. This study will examine whether addition of Kuvan to the standard of care at an early age in children with well controlled diets can lower blood Phe levels (ie, reach and maintain a goal of ≤ 240 micromole/L) and preserve neurocognitive functioning. In addition, this study will provide data on Kuvan exposure, rate of uptake, half life, and clearance in young children.