Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: Kuvan®
Intervention description: Kuvan® (sapropterin dihydrochloride) will be administered orally at a dose of 20 milligram per kilogram per day (mg/kg/day) once daily for 8 days. If there is 30 percent (%) decrease in blood phenylalanine levels from baseline at the end of Day 8, then treatment will be continued at the same dose for further 6 weeks.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 4 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: EMR 700733_510, Genetic disorder, Phenylketonuria, phenylalanine, Kuvan, sapropterin dihydrochloride

Summary:

      This is an open-label, non-comparative, Phase 3 study to evaluate the degree, frequency of
      response and safety of Kuvan® (sapropterin dihydrochloride) in subjects aged 4 to 18 years
      who have phenylketonuria and with elevated blood phenylalanine level of greater than or equal
      to 450 micromole per liter.
    

Eligibility criteria:

        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