Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptin™ Treatment in Subjects With Phenylketonuria

A Phase 2, Multicenter, Open-Label Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptin™ Treatment in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels

The primary objective is to evaluate the degree and frequency of response to Phenoptin™ (sapropterin dihydrochloride), as demonstrated by a reduction in blood phenylalanine (Phe) level among subjects with phenylketonuria (PKU) who have elevated Phe levels. A secondary objective of this study is to evaluate the safety of Phenoptin™ treatment in this subject population, and identify individuals in this subject population who respond to Phenoptin™ treatment with a reduction in blood Phe level.

Inclusion Criteria:

• Age >/= 8 years
• Blood Phe level >/= 450 umol/L at screening
• Clinical diagnosis of PKU with hyperphenylalaninemia documented by past medical history of at least one blood Phe measurement >/= 360 umol/L (6 mg/dL)
• Willing and able to provide written informed consent or, in the case of subjects under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained
• Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only)
• Male and Female subjects of childbearing potential childbearing potential (if sexually active and non-sterile) must be using acceptable birth control measures, as determined by the investigator, and willing to continue to use acceptable birth control measures while participating in the study
• Willing and able to comply with study procedures
• Willing to continue current diet unchanged while participating in the study

Exclusion Criteria:

• Perceived to be unreliable or unavailable for study participation or, if under the age of 18, have parents or legal guardians who are perceived to be unreliable or unavailable
• Use of any investigational agent within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments
• Pregnant or breastfeeding, or considering pregnancy
• ALT > 5 times the upper limit of normal (i.e., Grade 3 or higher based on World Health Organization Toxicity Criteria) at screening
• Concurrent disease or condition that would interfere with study participation or safety (e.g., seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, or insulin-dependent diabetes, or organ transplantation)
• Serious neuropsychiatric illness (e.g., major depression) not currently under medical control
• Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate)
• Concurrent use of levodopa
• Clinical diagnosis of primary BH4 deficiency