Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients

NCT ID: NCT01114737

Last Updated: 2016-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2013-03-31

Brief Summary

This double-blind, placebo-controlled, randomized study is designed to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuropsychiatric symptoms in subjects with PKU.

Detailed Description

Phenylketonuria (PKU) results from deficient phenylalanine hydroxylase (PAH) activity and leads to toxic phenylalanine (Phe) accumulation in patients with PKU causing mental retardation, microcephaly, delayed speech, seizures, psychiatric symptoms and behavioral abnormalities. Although for most PKU patients early initiation of dietary treatment prevents severe complications, discontinuation of dietary restrictions at an early age is associated with poor cognitive development and neuropsychiatric disorders are present even in early-treated and well controlled PKU patients.

This study, PKU-016, will be conducted in PKU patients to evaluate the therapeutic effects of sapropterin dihydrochloride on the symptoms of attention deficit hyperactivity disorder (ADHD), depression, and anxiety.

Conditions

Phenylketonuria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sapropterin dihydrochloride

Group Type: EXPERIMENTAL

Sapropterin dihydrochloride

Intervention Type: DRUG

A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact).

Tablet without active ingredient

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study.

Interventions

Sapropterin dihydrochloride

A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact).

Intervention Type: DRUG

Placebo

Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study.

Intervention Type: DRUG

Other Intervention Names

Kuvan; Phenoptin; BH4; 6R BH4

Eligibility Criteria

Inclusion Criteria

• ≥ 8 years of age
• Confirmed diagnosis of PKU
• Willing to continue current diet (typical diet for the 3 months prior to study entry) unchanged while participating in the study
• Willing and able to provide written, signed informed consent or in the case of subjects under the age of 18, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
• Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study and for at least 30 days following the last dose of sapropterin dihydrochloride
• Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or have had total hysterectomy.
• Willing and able to comply with all study procedure

Exclusion Criteria

• Has known hypersensitivity to sapropterin dihydrochloride or its excipients
• Subject breastfeeding at screening or planning to become pregnant (subject or partner) at any time during the study
• Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to the completion of all scheduled study assessments
• Received sapropterin dihydrochloride within 16 weeks of randomization
• Have initiated or adjusted medication for treatment of ADHD, depression, or anxiety ≤ 8 weeks prior to randomization
• Taking medication known to inhibit folate synthesis (eg, methotrexate)
• Any condition requiring treatment with levodopa or any PDE-5 inhibitor
• Concurrent disease or condition that would interfere with study participation, compliance or safety as determined by the Investigator
• Any condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suyash Prasad, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

La Jolla, California, United States

Los Angeles, California, United States

Palo Alto, California, United States

San Francisco, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Gainesville, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Indianapolis, Indiana, United States

Boston, Massachusetts, United States

Minneapolis, Minnesota, United States

Albany, New York, United States

Buffalo, New York, United States

Rochester, New York, United States

Chapel Hill, North Carolina, United States

Cleveland, Ohio, United States

Portland, Oregon, United States

Hershey, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Madison, Wisconsin, United States

Milwaukee, Wisconsin, United States

Calgary, Alberta, Canada

Edmonton, Alberta, Canada

Vancouver, British Columbia, Canada

Winnipeg, Manitoba, Canada

Halifax, Nova Scotia, Canada

Hamilton, Ontario, Canada

Kingston, Ontario, Canada

London, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Countries

United States; Canada

References

Grant ML, Jurecki ER, McCandless SE, Stahl SM, Bilder DA, Sanchez-Valle A, Dimmock D. Neuropsychiatric Function Improvement in Pediatric Patients with Phenylketonuria. J Pediatr. 2023 Sep;260:113526. doi: 10.1016/j.jpeds.2023.113526. Epub 2023 May 30.

Reference Type: DERIVED

PMID: 37263523 (View on PubMed)

Other Identifiers

PKU Ascend

Identifier Type: OTHER

Identifier Source: secondary_id

PKU-016

Identifier Type: -

Identifier Source: org_study_id