PKU, KUVAN
Conditions
Interventions
After parent(s)/guardian(s) have signed the
Independent Ethics Committee (IEC)-approved
informed consent form, subjects will be screened for eligibility to enter the study. Eligible study candidates w
2. Just a Phe-restricted diet.
They will then have their Phe levels checked twice weekly and will have their Phe intake adjusted every two weeks during the 26-week Study Period. Subjects will also r
Sponsors
In The Netherlands
1. University Medical Center Amsterdam
2. Academisch Ziekenhuis Maastricht
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female PKU infants and young children <4 years of age at the scheduled Day 1 visit of the 26-week Study Period (taking into consideration the maximum of 21 days in the Screening Period); 2. At least two previous blood Phe levels ≥ 400 μmol/L obtained on 2 separate occasions; 3. Previously responded, as assessed by the Investigator, to a BH4 test, if all 3 of the following criteria are satisfied: A. The BH4 dose was 20 mg/kg/day; B. The duration of the test was at least for 24 hours, and; C. Blood Phe levels decreased by at least 30%. NOTE: If a patient has not undergone a BH4 test prior to Screening, such a test must be performed during Screening, and all 3 of the above criteria must be satisfied for the subject to be eligible for entry into this study. 4. Defined level of dietary Phe tolerance consistent with the diagnosis of PKU; 5. Good adherence to dietary treatment, including prescribed dietary Phe restriction and prescribed amounts of Phe-free protein supplements and low- Phe foods; 6. Maintenance of blood Phe levels within the therapeutic target range of 120-360 μmol/L (defined as ≥120 to <360 μmol/L) over a 1-month period prior to Screening, as assessed by the Investigator; 7. Parent(s) and/or guardian(s) willing to comply with all study procedures, maintain strict adherence to the diet, and willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study procedures.
Exclusion criteria
Exclusion criteria: The exclusion criteria consist of: 1. Use of Kuvan®, Biopten®, or any unregistered preparation of tetrahydrobiopterin within the previous 30 days, unless for the purposes of a BH4 responsiveness test; 2. Previous exposure to Kuvan®, Biopten®, or any unregistered preparation of tetrahydrobiopterin for >30 days; 3. Known hypersensitivity to Kuvan® or its excipients; 4. Known hypersensitivity to other approved or nonapproved formulations of tetrahydrobiopterin; 5. Previous diagnosis of BH4 deficiency; 6. Current use of methotrexate, trimethoprim, or other dihydrofolate reductase inhibitors; 7. Current use of medications that are known to affect nitric oxide synthesis, metabolism or action; 8. Current use of levodopa; 9. Current use of experimental or unregistered drugs that may affect the study outcomes; 10. Inability to comply with study procedures; 11. Inability to tolerate oral intake; 12. History of organ transplantation; 13. Concurrent disease or condition that would interfere with study participation or increase the risk for adverse events, including seizure disorders, corticosteroid administration, active malignancy, diabetes mellitus, severe congenital heart disease, renal or hepatic failure; 14. Other significant disease that in the Investigator’s opinion would exclude the subject from the trial; 15. Any condition that, in the view of the Principal Investigator renders the subject at high risk for failure to comply with treatment or to complete the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dietary Phe tolerance after 26 weeks (6 months) of treatment with Kuvan® + a Phe-restricted diet, as compared to just a Phe-restricted diet alone. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Levels of blood Phe during the Study Period; 2. Change from Baseline (prior to enrolment) in dietary Phe tolerance after 26 weeks (6 months) treatment with Kuvan® + a Phe-restricted diet vs. just a Phe-restricted diet; 3. Blood pressure during the 26-week Study Period and the 3-year Extension Period; 4. Growth parameters (length or height, weight and maximal occipital-frontal head circumference) during the 26-week Study Period and the 3-year Extension Period; 5. Neuromotor developmental milestones and standardized neurodevelopment test results during the 26-week Study Period and the 3-year Extension Period; 6. Safety, including attention to age group-specific safety concerns (see Sections 3.12 and 7.5.1): A. Nature, incidence and severity of adverse events; B. Long-term safety for patients enrolled into the Extension Period; C. Incidence of hypophenylalaninemia (a blood Phe level <120 μmol/L), and; D. Changes from baseline in vital signs and clinical laboratory parameters. 7. PopPK endpoints will include: A. CL/f (apparent clearance); B. V/f (apparent volume of distribution); C. AUC0-∞ (area under the plasma concentration curve, time 0 to infinity); D. Cmax (maximum observed plasma concentration); E. Tmax (time to maximum plasma concentration), and; F. t1/2 (terminal elimination half-life). 8. PAH genotype. | — |
Contacts
Public ContactRalf Vis
Boeing Avenue 62-68
Outcome results
None listed