Clinical trial NCT01114737: Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Phenylketonuria
Keywords: Phenylketonuria
PKU
Kuvan
Sapropterin dihydrochloride
Neuropsychiatric disorder
ADHD
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2010-05-03
Enrollment: 206
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 13
timeFrame: Baseline to Week 13
measure: Number of Participants With a Score of 1 or 2 in Global Function Evaluation (CGI-I) From Baseline to Week 13.
timeFrame: 13 weeks
Secondary outcomes:
measure: Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 13
timeFrame: Baseline to Week 13
measure: Change in Hamilton Depression Rating Scale (HAM-D) Score From Baseline to Week 13
timeFrame: Baseline to Week 13
measure: Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 13
timeFrame: Baseline to Week 13
measure: Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 13
timeFrame: Baseline to Week 13
measure: Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Baseline to Week 13
timeFrame: Baseline to Week 13
measure: Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Week 13 to Week 26
timeFrame: Week 13 to Week 26
measure: Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Week 13 to Week 26
timeFrame: Week 13 to Week 26
measure: Change in Hamilton Depression Rating Scale (HAM-D) Score From Week 13 to Week 26
timeFrame: Week 13 to Week 26
measure: Change in Clinical Global Impression-Severity (CGI-S) From Week 13 to Week 26
timeFrame: Week 13 to Week 26
measure: Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Week 13 to Week 26
timeFrame: Week 13 to Week 26
measure: Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Week 13 to Week 26
timeFrame: Week 13 to Week 26
measure: Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in Hamilton Rating Scale For Depression (HAM-D) Score From Baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Baseline to Week 26
timeFrame: Baseline to Week 26
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington DC
country: United States
state: District of Columbia
city: Gainesville
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Albany
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: BioMarin Pharmaceutical
name: Suyash Prasad, MD
role: STUDY_DIRECTOR
References: