Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: sapropterin dihydrochloride
Intervention description: 5-20mg/kg/day orally, dose may be adjusted up or down as needed at the discretion of the investigator in increments of 5mg/kg/day.
Intervention MeSH terms: Verapamil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 111.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: PKU

Summary:

      The objective of this study is to evaluate the safety of long-term treatment with Phenoptin
      in subjects with phenylketonuria (PKU) who participated in Phase 3 clinical studies with
      Phenoptin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participation in study PKU-004 or PKU-006

          -  Willing and able to provide written, signed informed consent or, in the case of
             subjects under the age of 18 years, provide written assent (if required) and written
             informed consent by a parent or legal guardian, after the nature of the study has been
             explained, and prior to any research-related procedures

          -  Negative urine pregnancy test at screening (females of child-bearing potential)

          -  Willing and able to comply with all study procedures

        Exclusion Criteria:

          -  Non-responsive to prior treatment with Phenoptin based on participation in PKU-004 or
             PKU-006

          -  Perceived to be unreliable or unavailable for study participation or, if under the age
             of 18 years, have parents or legal guardians who are perceived to be unreliable or
             unavailable

          -  Terminated early from PKU-004 or PKU-006, except for subjects in PKU-004 that rolled
             into PKU-008 at Week 22, subjects in PKU-006 that rolled into PKU-008 at Week 10, or
             subjects in PKU-006 that terminated due to elevated Phe levels following dietary Phe
             increases

          -  Use of any investigational product other than Phenoptin within 30 days prior to
             screening, or anticipated requirement for any investigational agent prior to
             completion of all scheduled study assessments

          -  Positive urine pregnancy test at screening (non-sterile females of child-bearing
             potential only), already known to be pregnant or breastfeeding or planning a pregnancy
             in self or partner during the study

          -  Female subjects of childbearing potential must be using an effective method of birth
             control, as determined by the PI, and willing to continue to use acceptable birth
             control measures

          -  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)

          -  Any condition that, in the view of the PI, renders the subject at high risk from
             treatment compliance and/or completing the study

          -  ALT > 2 times the upper limit of normal (i.e., Grade 1 or higher based on World Health
             Organization Toxicity Criteria) at screening (see Appendix 2)

          -  Serious neuropsychiatric illness (e.g., major depression) not currently under medical
             control

          -  Prior history of organ transplantation

          -  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