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Trial record 15 of 20 for:    PKU | Boston, Massachusetts, U.S.

Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU (PKU-015)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00838435
Recruitment Status : Completed
First Posted : February 6, 2009
Last Update Posted : January 24, 2019
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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.

Condition or disease Intervention/treatment Phase
Phenylketonuria Drug: sapropterin dihydrochloride Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : February 2009
Actual Primary Completion Date : September 14, 2018

Arm Intervention/treatment
Experimental: 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.
Drug: 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.
Other Names:
  • Kuvan
  • Phenoptin
  • BH4
  • 6R BH4

Primary Outcome Measures :
  1. 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 Measures :
  1. To evaluate the long term safety of Kuvan in the study population [ Time Frame: 7 years ]
  2. To evaluate the effect of Kuvan on growth parameters in the study population [ Time Frame: 7 years ]
  3. 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 ]
  4. To evaluate the population pharmacokinetics of Kuvan in young children [ Time Frame: 4 Weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00838435

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United States, California
La Jolla, California, United States
Orange, California, United States
United States, Florida
Tampa, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Ohio
Cleveland, Ohio, United States
Columbus, Ohio, United States
United States, Pennsylvania
Hershey, Pennsylvania, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Canada, Alberta
Edmonton, Alberta, Canada
Canada, British Columbia
Vancouver, British Columbia, Canada
Canada, Manitoba
Winnipeg, Manitoba, Canada
Canada, Ontario
Hamilton, Ontario, Canada
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Sainte-Fo, Quebec, Canada
Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: Joshua Lilienstein, M.D. BioMarin Pharmaceutical

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Responsible Party: BioMarin Pharmaceutical Identifier: NCT00838435    
Other Study ID Numbers: PKU-015
First Posted: February 6, 2009    Key Record Dates
Last Update Posted: January 24, 2019
Last Verified: January 2019
Keywords provided by BioMarin Pharmaceutical:
Neurocognitive Function
Additional relevant MeSH terms:
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Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents