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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00838435
• Date of registration: 05/02/2009
• Prospective Registration: No
• Primary sponsor: BioMarin Pharmaceutical
• Public title: Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU PKU-015
• Scientific 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
• Date of first enrolment: February 2009
• Target sample size: 95
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00838435
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, United States

Contacts

• Name: Joshua Lilienstein, M.D.
• Affiliation: BioMarin Pharmaceutical

Key inclusion & exclusion 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 < 6 months old at Screening
must be considered controlled and stable by the Investigator

- Willing to adhere to a prescribed Phe restricted diet in order to maintain blood Phe
concentrations within the recommended ranges established at the subject's study site

- Age 0 to 6 years old, inclusive, at Screening

- Parent(s) or guardian(s) willing and able to provide written, signed informed consent
after the nature of the study has been explained, and prior to any research-related
procedures

- Parent(s) or guardian(s) willing and able to comply with all study procedures

- Female subjects of childbearing potential (as determined by the investigator) and
sexually mature male subjects willing to use a medically accepted method of
contraception throughout the study. Female subjects of childbearing potential willing
to undergo periodic pregnancy tests during the course of the study

Exclusion Criteria:

- Established diagnosis of primary tetrahydrobiopterin (BH4) deficiency

- Known hypersensitivity to Kuvan or its excipients

- History of organ transplantation

- Perceived to be unreliable or unavailable for study participation or to have parents
or legal guardians who are perceived to be unreliable or unavailable

- Use of methotrexate or other medications that inhibit folate metabolism

- Serious neuropsychiatric illness (eg, major depression) not currently under medical
control

- Use of Kuvan or any investigational agent within 30 days prior to Screening, or known
requirement for any investigational agent prior to completion of all scheduled study
assessments

- Concurrent disease or condition that would interfere with study participation or
safety (eg, seizure disorder, oral steroid-dependent asthma or other condition
requiring oral or parenteral corticosteroid administration, or insulin dependent
diabetes)

- Any condition that, in the view of the Principal Investigator (PI), renders the
subject at high risk for failure to comply with treatment or to complete the study

- Use of phosphodiesterase type 5 inhibitor, often shortend to PDE5 inhibitor (eg,
sildenafil citrate, vardenafil, tadalafil, avanafil, lodenafil, mirodenafil, udenafil)



Age minimum: N/A
Age maximum: 6 Years
Gender: All

Health Condition(s) or Problem(s) studied

Phenylketonuria

Intervention(s)

Drug: sapropterin dihydrochloride

Primary Outcome(s)

To evaluate the long term efficacy of Kuvan in preserving neurocognitive function in children with PKU when treatment is initiated at 0-6 years [Time Frame: 7 years]

Secondary Outcome(s)

To evaluate the population pharmacokinetics of Kuvan in young children [Time Frame: 4 Weeks]

To evaluate baseline neurocognitive function for all Kuvan-responsive subjects and 6 month Bayley III data for subjects who are 0-2 years old at enrollment [Time Frame: 6 Months]

To evaluate the long term safety of Kuvan in the study population [Time Frame: 7 years]

To evaluate the effect of Kuvan on growth parameters in the study population [Time Frame: 7 years]

Secondary ID(s)

PKU-015

Source(s) of Monetary Support

Please refer to primary and secondary sponsors