Phenylketonuria MedDRA version: 18.1 Level: LLT Classification code 10034873 Term: Phenylketonuria (PKU) System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Kuvan
Product Name: Sapropterin Dihydrocholoride
Product Code: NAP
Pharmaceutical Form: Soluble tablet
INN or Proposed INN: SAPROPTERIN
CAS Number: 62989337
Other descriptive name: tetrahy
Sponsors
BioMarin International Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female PKU infants and young children =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 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 non-approved 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 |
|---|---|
| Main Objective: 1.Evaluate the efficacy after 26 weeks of Kuvan® treatment + Phe-restricted diet therapy in increasing dietary Phe tolerance, as compared to dietary therapy alone in <4 year-old infants and children with phenylketonuria (PKU). Phe tolerance will be defined as the amount of dietary Phe (mg/kg/day) ingested while maintaining blood Phe levels within the range of 120-360 µmol/L (defined as =120 to < 360 µmol/L). 2.Evaluate the safety after 26 weeks of Kuvan® treatment in <4 year-old infants and children with PKU. 3.Evaluate BH4 (tetrahydrobiopterin; sapropterin) blood levels via scheduled PopPK samplings. ;Secondary Objective: 1.Evaluate blood Phe levels for all subjects during the 26-week Study Period. 2.Evaluate the effectiveness of Kuvan® treatment in increasing dietary Phe tolerance, as compared to pre-Kuvan® treatment during the 26-week Study Period in <4 year-old infants and children with PKU. 3.Assess neurodevelopmental function during Kuvan® treatment, as compared to dietary treatment alone, during the 26-week Study Period in <4 year-old infants and children with PKU. 4.Assess potential effects on blood pressure during the 26-weeks Study Period and the 3-year Extension Period. 5.Assess potential effects on growth during the 26-weeks Study Period and the 3-year Extension Period. 6.Evaluate long-term safety, neurodevelopmental outcomes, dietary Phe tolerance, and blood Phe levels in the 3-year Extension Period. 7.Investigate in BH4-responsive individuals the predictive value of the phenylalanine hydroxylase (PAH) genotype. ;Primary end point(s): 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. ;Timepoint(s) of evaluation of this end point: 26 weeks (6 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Levels of blood Phe during the 26-week Study Period and the 3-year Extension Period. -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. -Dietary Phe tolerance during the 3-year Extension Period. -Blood pressure during the 26-week Study Period and the 3-year Extension Period. -Growth parameters (length or height, weight, and maximum occipital-frontal head circumference) during the 26-week Study Period and the 3-year Extension Period. -Neuromotor developmental milestones and standardized neurodevelopment test results during the 26-week Study Period and the 3-year Extension Period. -Safety, including attention to age group-specific safety concerns: -Nature, incidence, and severity of adverse events; -Long-term safety for patients enrolled into the Extension Period. -Incidence of hypophenylalaninemia (blood Phe <120 µmol/L); -Changes from baseline in vital signs and clinical laboratory parameters. Population PK endpoints will include: -CL/f (apparent clearance); -V/f (apparent volume of distribution); -AUC0-8 (area under the plasma concentration curve, time 0 to infinity); -Cmax (maximum observed plasma concentration); -Tmax (time to maximum plasma concentration); and -t1/2 (terminal elimination half-life). -PAH genotype.;Timepoint(s) of evaluation of this end point: At the end of study part (26 weeks) or at the end of the extension period | — |
Countries
Austria, Belgium, Czech Republic, Germany, Italy, Netherlands, Portugal, Slovakia, Turkey, United Kingdom
Contacts
Public ContactMirko M. Essing, MD
BioMarin International Ltd
Outcome results
None listed