Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels

The primary objective of this study is to evaluate the efficacy of Phenoptin™ (sapropterin dihydrochloride) in reducing blood phenylalanine (Phe) levels in subjects with phenylketonuria.

Inclusion Criteria:

• 8 years of age and older
• Received at least 7 out of 8 scheduled doses in Study PKU 001
• Responsive to Phenoptin™ in Study PKU-001, defined as a reduction in blood Phenylalanine level of >/=30% compared with baseline
• Blood Phenylalanine level >/=450 μmol/L at screening
• 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 (females of child-bearing potential)
• Male and Female subjects of childbearing potential (if sexually active) 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 other than Phenoptin™ within 30 days prior to screening, or requirement for any investigational agent or investigational 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 recipient)
• Serious neuropsychiatric illness (e.g., major depression) not currently under medical management
• 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