Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder by a mutation in the gene for the enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional. Left untreated, the disease will result in high concentrations of phenylalanine (Phe) in blood and tissues, likely resulting in severe mental retardation and behavioural problems. Treatment focusus on the restriction of dietary phenylalanine intake with supplementation of a synthetic phenylalaninefree amino acid mixture.
Conditions
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Males and females 4-12 years of age. - Diagnosed with phenylketonuria by newborn screening. - Tested to be sapropterin responsive. - Under good metabolic control; defined as 2/3 or 67% of the blood phenylalanine levels within target ranges during the last year. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Concomitant disease which may preclude the participation in the study in the judgment of the investigator. - Intercurrent illness which might influence the blood phenylalanine levels. - Concomitant medication as mentioned in the Kuvan® SPC. - Known hypersensitivity to Kuvan® or its excipients. - Known hypersensitivity to other approved or non-approved formulations of tetrahydrobiopterin. - Non-compliance with study procedures in the judgement of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To measure the effect of sapropterin on diurnal and day to day variations of blood phenylalanine concentrations.;Secondary Objective: - To measure the effect of sapropterin on diurnal and day to day variations of blood tyrosine concentrations. - To measure the effect of sapropterin on diurnal and day to day variations of blood phenylalanine/tyrosine ratios.;Primary end point(s): The mean standard deviations of the blood phenylalanine concentrations measured four times a day of 2 consecutive days and once a day on 8 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period.;Timepoint(s) of evaluation of this end point: In both study periods blood sampling is scheduled for the first six days once a day (7-8 am) and four times daily (7-8 am, 12-1 pm, 5-6 pm and bedtime) on the two days thereafter, in total 28 samples per patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The mean standard deviations of the blood tyrosine concentrations measured once a day on 8 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period. - The mean standard deviations of the blood tyrosine concentrations measured four times a day of 2 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period. - The mean standard deviations of the blood phenylalanine/tyrosine ratios measured once a day on 8 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period. - The mean standard deviations of the blood phenylalanine/tyrosine concentrations measured four times a day of 2 consecutive days of all participants compared between the sapropterin + diet treatment period and the diet alone treatment period.;Timepoint(s) of evaluation of this end point: In both study periods blood sampling is scheduled for the first six days once a day (7-8 am) and four times daily (7-8 am, 12-1 pm, 5-6 pm and bedtime) on the two days thereafter, in total 28 samples per patient. | — |
Countries
Netherlands
Contacts
Public ContactIndependent expert
University Medical Center Groningen
Outcome results
None listed