(PKU016) A double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuropsychiatric symptoms in subjects with phenylketonuria. (IRB# 34121)
Patricia L. Gordon, MD
The primary objective of this study is to: • Evaluate the therapeutic effects of sapropterin dihydrochloride on the symptoms of ADHD and global function of subjects when compared to placebo in subjects with a confirmed diagnosis of PKU who have a blood Phe level reduction after sapropterin dihydrochloride treatment (defined as a mean decrease of ≥ 20% in blood Phe levels during their first 4 weeks of sapropterin dihydrochloride treatment).
≥ 12 years of age
Confirmed diagnosis of PKU with at least 1 documented blood Phe level ≥ 360 μmol/L within 6 months prior to Screening
A score of 4 or above on CGI-S at Screening
Willing to continue current diet (typical diet for the 3 months prior to study entry) unchanged while participating in the study
Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
Has known hypersensitivity to sapropterin dihydrochloride or its excipients
Breastfeeding at screening or planning to become pregnant (self 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
Additional Study Details:
What is expected of me and my child?
Eligible subjects will be stratified on the basis of the presence of symptoms of ADHD (yes or no), age (< 18 or ≥ 18 years old), and use of ADHD medication (yes or no), randomized 1:1 to receive sapropterin dihydrochloride or placebo, and treated for 13 weeks (Randomized Treatment Period).
All subjects completing the Randomized Treatment Period will then be treated with open label sapropterin dihydrochloride (Open-Label Treatment Period) for an additional 13 weeks. All subjects will undergo clinical assessments including the ADHD RS/ASRS at Screening (for stratification by the presence of symptoms of ADHD), and at Weeks 4, 8, 13, and 26, HAM-D and HAM-A (at Baseline and at Weeks 4, 8, 13, and 26), and CGI (CGI-S at Screening and CGI-S and CGI-I at Weeks 4, 8, 13, and 26). In the event of a positive response to question 3 of the HAM-D, the Columbia Suicide Severity Rating Scale (C-SSRS) will be administered.
For subjects randomized to sapropterin dihydrochloride treatment during the first 13 weeks, Phe levels obtained weekly during the first 4 weeks of treatment will be used to determine the efficacy analysis population based on the level of Phe level reduction after sapropterin dihydrochloride treatment. For subjects randomized to placebo that complete the Randomized Treatment Period, Phe levels obtained weekly during the first 4 weeks of sapropterin dihydrochloride treatment in the Open-Label Treatment Period (Weeks 14-17) will be used to determine the efficacy analysis population based on the level of Phe level reduction after sapropterin dihydrochloride treatment. Phe level reduction after sapropterin dihydrochloride treatment will be defined by a mean decrease of ≥ 20% in blood Phe levels after the first 4 weeks of treatment. In addition, blood Phe levels will also be measured throughout the study.
Subjects will be required to maintain dietary Phe intake levels for the entire duration of the study that are consistent with their dietary intake during the 3 months prior to study entry.