Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria

Inclusion Criteria: * Willing and able to provide written informed consent (for children under 18 years old the parent\[s\]/guardians give informed consent, subjects 14-17 years old give additionally their own written informed consent) * Age of 4 - 18 years, inclusive * Confirmed clinical and biochemical hyperphenylalaninemia due to phenylketonuria documented by past medical history with at least 2 blood phenylalanine level greater than or equal to 400 micromole per liter obtained in 2 separate occasions * Blood phenylalanine level at screening greater than or equal to 450 micromole per liter (mean of two measurements) * For women of childbearing potential, a negative urine pregnancy test is required at screening and willingness to use a highly effective method of contraception is required while participating in the study * Subject and/or the parent/guardian willing and able to comply with study procedures * Subject and/or the parent/guardian willing to continue current diet unchanged during the 8 days response test and to adapt the diet according to phenylalanine therapeutic target range during the 6 week treatment period Exclusion Criteria: * Subject already assessed for responsiveness to sapropterin dihydrochloride or other tetrahydrobiopterin (BH4) * Used any investigational agent other than Kuvan® (sapropterin dihydrochloride) within 30 days of screening, or required any investigational agent or vaccine prior to completion of all scheduled study assessments * Pregnant or breastfeeding, or considering pregnancy * Concurrent disease or conditions that would interfere with study participation or safety (for example, seizure disorder, asthma or other condition requiring oral or parenteral corticosteroid administration, insulin-dependent diabetes, or organ transplantation recipient) * Concurrent use of required concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate), levodopa, phosphodiesterase type-5 (PDE-5) inhibitors (such as, sildenafil, vardenafil or tadalafil), medications that are known to affect nitric oxide synthesis metabolism or action * Any conditions, that, in the view of the Principal Investigator renders the subject at high risk for failure to comply with treatment or to complete the study * Clinical diagnosis of primary BH4 deficiency * Known hypersensitivity to Kuvan® (sapropterin dihydrochloride) or its excipients or to other approved or non-approved formulation of tetrabiopterin