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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00838435
First received: February 5, 2009
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

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 Intervention Phase
Phenylketonuria
Drug: sapropterin dihydrochloride
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the long term safety of Kuvan in the study population [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
  • To evaluate the effect of Kuvan on growth parameters in the study population [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate the population pharmacokinetics of Kuvan in young children [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 230
Study Start Date: February 2009
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00838435

Locations
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
Investigators
Study Director: Suyash Prasad, M.D. BioMarin Pharmaceutical
  More Information

No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT00838435     History of Changes
Other Study ID Numbers: PKU-015
Study First Received: February 5, 2009
Last Updated: November 28, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by BioMarin Pharmaceutical:
Phenylketonuria
PKU
Kuvan
Phenoptin
Biopten
Neurocognitive Function
Phenylalanine

Additional relevant MeSH terms:
Phenylketonurias
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

ClinicalTrials.gov processed this record on August 28, 2014