Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: Sapropterin dihydrochloride; Placebo
Intervention description: A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact).; Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study.
Intervention MeSH terms: Verapamil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 206.0
Sex: All
Minimum age: 8 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Phenylketonuria; PKU; Kuvan; Sapropterin dihydrochloride; Neuropsychiatric disorder; ADHD

Summary:

      This double-blind, placebo-controlled, randomized study is designed to evaluate the safety
      and therapeutic effects of sapropterin dihydrochloride on neuropsychiatric symptoms in
      subjects with PKU.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 8 years of age

          -  Confirmed diagnosis of PKU

          -  Willing to continue current diet (typical diet for the 3 months prior to study entry)
             unchanged while participating in the study

          -  Willing and able to provide written, signed informed consent or in the case of
             subjects under the age of 18, provide written assent (if required) and written
             informed consent by a legally authorized representative after the nature of the study
             has been explained, and prior to any research-related procedures

          -  Sexually active subjects must be willing to use an acceptable method of contraception
             while participating in the study and for at least 30 days following the last dose of
             sapropterin dihydrochloride

          -  Females of childbearing potential must have a negative pregnancy test at screening and
             be willing to have additional pregnancy tests during the study. Females considered not
             of childbearing potential include those who have been in menopause at least 2 years,
             or had tubal ligation at least 1 year prior to screening, or have had total
             hysterectomy.

          -  Willing and able to comply with all study procedure

        Exclusion Criteria:

          -  Has known hypersensitivity to sapropterin dihydrochloride or its excipients

          -  Subject breastfeeding at screening or planning to become pregnant (subject or partner)
             at any time during the study

          -  Use of any investigational product or investigational medical device within 30 days
             prior to screening, or requirement for any investigational agent prior to the
             completion of all scheduled study assessments

          -  Received sapropterin dihydrochloride within 16 weeks of randomization

          -  Have initiated or adjusted medication for treatment of ADHD, depression, or anxiety ≤
             8 weeks prior to randomization

          -  Taking medication known to inhibit folate synthesis (eg, methotrexate)

          -  Any condition requiring treatment with levodopa or any PDE-5 inhibitor

          -  Concurrent disease or condition that would interfere with study participation,
             compliance or safety as determined by the Investigator

          -  Any condition that, in the view of the Investigator, places the subject at high risk
             of poor treatment compliance or of not completing the study