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

Purpose

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.

Condition	Intervention	Phase
Phenylketonuria	Drug: Sapropterin dihydrochloride Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Double-blind, Placebo-controlled, Randomized Study to Evaluate the Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Subjects With Phenylketonuria

Resource links provided by NLM:

Genetics Home Reference related topics: argininosuccinic aciduria citrullinemia N-acetylglutamate synthase deficiency ornithine translocase deficiency phenylketonuria succinic semialdehyde dehydrogenase deficiency tetrahydrobiopterin deficiency

MedlinePlus related topics: Phenylketonuria

Drug Information available for: Sapropterin Sapropterin dihydrochloride

U.S. FDA Resources

Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:

Evaluate the therapeutic effects of sapropterin dihydrochloride on the symptoms of ADHD and on global function compared to placebo, in subjects with a blood Phe level reduction after treatment. [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
ADHD change will be measured as a change in ADHD from baseline to week 13 using the Attention-Deficit Hyperactivity Disorder Rating Scale and Adult ADHD Self-Report Scale (ADHD RS/ASRS) measurement. Global function will be measured as a change in global function using the Clinical Global Impression-Improvement (CGI-I) scale rating compared from baseline to week 13.

Secondary Outcome Measures:

Evaluate the therapeutic effects of sapropterin dihydrochloride on the symptoms of anxiety and depression compared to placebo, in subjects with a blood Phe level reduction after treatment. [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Evaluate the durability of any therapeutic effects of sapropterin dihydrochloride on neuropsychiatric symptoms and global function of subjects who have a blood Phe level reduction after treatment. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Determine if sapropterin dihydrochloride has a therapeutic effect on neuropsychiatric symptoms in PKU patients who do not have a blood Phe reduction after treatment. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Assess the safety of sapropterin dihydrochloride when administered as therapy to these patients. [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	200
Study Start Date:	June 2010
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sapropterin dihydrochloride	Drug: Sapropterin dihydrochloride A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact). Other Names: Kuvan Phenoptin BH4 6R BH4
Placebo Comparator: Tablet without active ingredient	Drug: Placebo Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study.

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.

Eligibility

Ages Eligible for Study:	8 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01114737

Show 39 Study Locations

Sponsors and Collaborators

BioMarin Pharmaceutical

Investigators

Study Director:

Suyash Prasad, MD

BioMarin Pharmaceutical

More Information

No publications provided

Responsible Party:	BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:	NCT01114737 History of Changes
Other Study ID Numbers:	PKU-016, PKU Ascend
Study First Received:	April 27, 2010
Last Updated:	November 28, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada

Keywords provided by BioMarin Pharmaceutical:

Phenylketonuria
PKU
Kuvan

Sapropterin dihydrochloride
Neuropsychiatric disorder
ADHD

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

Verapamil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013