Phenylketonuria MedDRA version: 16.0 Level: LLT Classification code 10034873 Term: Phenylketonuria (PKU) System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Kuvan®
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Sapropterin
CAS Number: 62989-33-7
Other descriptive name: SAPROPTERIN DIHYDROCHLORIDE
Concentration unit: mg milligram(s)
Co
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion 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 Phe levels = 600 µmol/L. • Willingness to use a highly effective method of contraception is required during the study and follow-up periods. For women of childbearing potential: a negative urine pregnancy test is required at the end of screening. • Aged = 18 to 29 years, inclusive. • Mean blood Phe levels 600 to 1000 µmol/L during 12 months preceding inclusion in the study. The mean should be calculated from at least 3 blood Phe values over the last 12 months. Screening blood Phe 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 = 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Subjects with tetrahydrobiopterin (BH4) deficiency. • Previous exposure to sapropterin or BH4 for > 30 days (or exposure to sapropterin or BH4 for = 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 (e.g., 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 (e.g., methotrexate, trimethoprim), medications that are known to affect nitric oxide synthesis (e.g., 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 in another clinical trial or who participated in a previous clinical trial within 30 days prior to screening. • Legal incapacity or limited legal capacity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Exploratory Objectives: - effect of sapropterin on executive function (EF), attention and processing speed - assess whether a cognitive abilities composite score specific to PKU can be created - effect of sapropterinon on daily life behavior - long-term efficacy of sapropterin in reducing blood phenylalanine (Phe) levels - evaluation of within-subject variability in Phe levels over the last 20 weeks of treatment - effect of sapropterin on the Phe/tyrosine (Tyr) ratio - correlation between cognitive performance or score on scales and biological parameters (mean Phe levels over study period, mean change in Phe levels, concurrent blood Phe levels [at moment of test], Phe/Tyr ratio or variability in Phe levels) - evaluate the relationship between response to sapropterin and phenylalanine hydroxylase (PAH) genotype Safety Objective: To assess the safety and tolerability of sapropterin taken as intact tablets in young adults with PKU over a 26-week period.;Main Objective: The purpose of this pilot trial is to assess the effect of sapropterin on the cognitive abilities of young adults with phenylketonuria (PKU).;Primary end point(s): As this trial is exploratory in nature, no statistical endpoints were defined as primary or secondary.;Timepoint(s) of evaluation of this end point: Not applicable. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): As this trial is exploratory in nature, no statistical endpoints were defined as primary or secondary.;Timepoint(s) of evaluation of this end point: Not applicable. | — |
Countries
Belgium, France, Germany, Italy, Netherlands, Spain, Switzerland
Contacts
Public ContactCommunication Center Merck KGaA
Merck KGaA
Outcome results
None listed