Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: Sapropterin; Placebo
Intervention description: Sapropterin tablets will be administered orally once daily at a dose of 20 milligram per kilogram (mg/kg) during both the 2-Week response test period and 24-Week study period.; Sapropterin tablets will be administered orally once daily at a dose of 20 milligram per kilogram (mg/kg) during both the 2-Week response test period and Placebo tablets matching to sapropterin will be administered orally once daily during the 24-Week study period.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 29 Years
Healthy volunteers: No
Keywords: Phenylketonuria; Sapropterin; Placebo; Cognitive Abilities; Kuvan®

Summary:

      This is a Phase 2a multicenter, double-blind, placebo-controlled, randomized, 2-arm pilot
      trial designed to assess the effect of sapropterin on cognitive abilities in young adults
      with Phenylketonuria (PKU) over a 26-week treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent given before any trial-related activities are carried out

          -  Women or men with documented PKU diagnosed by at least two phenylalanine levels equal
             or greater than 600 micromole per liter (mcmol/L)

          -  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 during the study and follow-up periods

          -  Aged greater than or equal to (>=) 18 to 29 years, inclusive

          -  Mean blood phenylalanine levels 600 to 1000 mcmol/L during 12 months preceding
             inclusion in the study. The mean should be calculated from at least 3 blood
             phenylalanine values over the last 12 months. Screening blood phenylalanine level can
             be one of these values. There should be at least one value dated between Month -12 and
             -6 before Screening and at least one value dated between Month -6 and Screening

          -  An intelligence quotient (IQ) score greater than or equal to 85, assessed a maximum of
             2 years before screening with an age-appropriate Wechsler scale. If no IQ test result
             is available, IQ testing must be performed as part of Screening using an
             age-appropriate Wechsler scale before the subject can be included

          -  Subjects willing to comply with all study procedures, including willingness to
             continue current dietary recommendations during the whole trial duration

        Exclusion Criteria:

          -  Subjects with tetrahydrobiopterin (BH4) deficiency

          -  Previous exposure to sapropterin or BH4 for greater than 30 days (or exposure to
             sapropterin or BH4 for less than or equal to 30 days but within the previous 6 months
             prior to Screening visit)

          -  Subjects who, according to the Investigator, will not be able to comply with study
             procedures and computerized neuropsychological testing

          -  Any significant illness which, according to the Investigator, might preclude
             participation in the study (including neurological disease, cardio-vascular disease,
             history of seizure, predisposition to convulsions, renal or hepatic insufficiency, and
             active malignancy)

          -  Any significant illness, medication or substance abuse which, according to the
             Investigator, might affect cognitive function and cognitive testing (for example,
             significant visual or motor impairment, history of major head trauma, history of
             stroke, alcoholism, drug dependency, psychological disorder requiring chronic use of
             psychotropic medications such as anxiolytics, antidepressants, antipsychotic
             medication, mood stabilizers, and hypnotics)

          -  Concomitant forbidden medication as described in the Kuvan® Summary of Product
             Characteristics, namely, inhibitors of dihydrofolate reductase (for example,
             methotrexate, trimethoprim), medications that are known to affect nitric oxide
             synthesis (for example, glyceryl trinitrate, isosorbide dinitrate, sodium
             nitroprusside, molsidomin, phosphodiesterase type 5 inhibitors, and minoxidil), and
             levodopa, as it may cause increased excitability and irritability

          -  Known hypersensitivity to sapropterin or any ingredients in the product's formulation,
             or to other approved or non-approved formulations of BH4

          -  Subjects who have undergone cognitive neuropsychological testing similar to that to be
             performed as part of this trial with the following time limits: tasks with limited
             practice effect performed in the last 6 months, and tasks with important practice
             effect (such as tasks involving development of strategies) performed in the year
             preceding inclusion in the trial. Whether a task falls into one or the other category
             is left to Investigator judgment

          -  Female subjects who are pregnant or in the lactation period

          -  Subjects currently participating to another clinical trial or who participated in a
             previous clinical trial within 30 days prior to screening

          -  Legal incapacity or limited legal capacity