Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU

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Disease Information

Descriptive Information
Brief Title † Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
Official Title † A Phase 3b Open-Label Study to Evaluate the Effect of Kuvan® on Neurocognitive Function, Maintenance of Blood Phenylalanine Concentrations, Safety, and Population Pharmacokinetics in Young Children With Phenylketonuria
Brief Summary This multicenter, open label study is designed to evaluate the safety of Kuvan® and its effect on neurocognitive function, blood Phe concentration, and growth in children with PKU who are 0-6 years old.
Detailed Description Rigorous control of diet is typically advocated in children 4 years and under with PKU because brain sensitivity to high Phe concentrations is expected to be greatest during these years of rapid neurocognitive development. Prolonged high blood Phe concentrations are neurotoxic and lead to impairment of intelligence and other brain functions (such as attentiveness). Reduction of blood Phe concentrations through dietary control is an important determinant of long-term neurologic outcome in PKU patients, and reduction of blood Phe concentrations in patients with PKU has been shown to decrease the long term risk of neurologic injury. It is difficult for many patients to maintain reduced blood Phe, and many patients with PKU experience some degree of neurological impairment despite efforts to maintain dietary Phe control. The strongest determinant of intelligence quotient (IQ) and cognitive function is compliance with blood Phe control. Several clinical studies with Kuvan have already demonstrated efficacy in reducing blood Phe in subjects older than 4 years. This study will examine whether addition of Kuvan to the standard of care at an early age in children with well controlled diets can lower blood Phe levels (ie, reach and maintain a goal of ≤ 240 micromole/L) and preserve neurocognitive functioning. In addition, this study will provide data on Kuvan exposure, rate of uptake, half life, and clearance in young children.
Study Phase Phase 3
Study Type † Interventional
Study Design †
Primary Outcome Measure † To evaluate the long term efficacy of Kuvan in preserving neurocognitive function in children with PKU when treatment is initiated at 0-6 years
Secondary Outcome Measure † To evaluate the long term safety of Kuvan in the study population
Condition † Phenylketonuria
Intervention † Drugsapropterin dihydrochloride
Study Arms / Comparison Groups sapropterin dihydrochloride A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 230
Start Date † February 2009
Completion Date January 2020
Primary Completion Date August 2019
Eligibility Criteria † Inclusion Criteria: - Established diagnosis of PKU with hyperphenylalaninemia (HPA) documented in the medical record by at least 2 blood Phe concentrations greater than or equal to 360 micromole/L (6 mg/dL) taken at least 3 days apart - Documented blood Phe control (defined by the standard used at each treatment center) prior to study enrollment, if applicable (eg, the subject is old enough for these data to be collected); blood Phe concentrations for subjects
Gender All
Ages N/A - 6 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries † Canada
Administrative Information
NCT ID † NCT00838435
Organization ID PKU-015
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † BioMarin Pharmaceutical
Collaborators ††
Investigators † Study Director: Joshua Lilienstein, M.D., BioMarin Pharmaceutical
Information Provided By
Verification Date April 2017
First Received Date † February 5, 2009
Last Updated Date April 5, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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