Clinical trial NCT01908192: Adaptive Phase II Study to Evaluate the Safety & Efficacy of NaBen®
Official title: An Adaptive, Phase IIb/III, Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy OF NaBen® , A D-Amino Acid Oxidase Inhibitor, as an Add-on Treatment for Schizophrenia in Adolescents
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Schizophrenia
Keywords: Sodium Benzoate
Schizophrenia
Adolescent
Antipsychotic
Anti-psychotic
NMDA
NaBen
pediatric
Lead sponsor: SyneuRx International (Taiwan) Corp
Sponsor class: INDUSTRY
First posted: 2013-07-25
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if NaBen® is a safe and effective add-on treatment for schizophrenia in adolescents.

Detailed description: This is a two-part, multi-center, prospective, randomized, placebo-controlled, parallel-group study, in which adolescent subjects with schizophrenia will be enrolled. Overall, eligible subjects will be randomized in a pre-defined 1:1 ratio to NaBen® or placebo.

This study will be conducted in two parts:

In Part 1 (Phase IIb) of the study, 76 subjects (\~ 60% of the total planned subjects) will be randomized in a 1:1 ratio (NaBen® or placebo), of which 38 subjects will be randomized to the NaBen® group and 38 subjects to the placebo group. An interim analysis (IA) will be conducted after the randomization of the 76th subject in Part 1 of the study. The data will be analyzed after all enrolled subjects in Part 1 of the study complete Visit 5 (week 6) or are withdrawn from the study, whichever occurs first. The data from IA will be reviewed by an independent Data Safety and Monitoring Committee (DSMC) that will be responsible for the review of the data from the Part 1 (Phase IIb) of the study for both safety and the effectiveness.

In Part 2 (Phase III) of the study, a total of 50 subjects will be randomized, of which 25 subjects will be randomized to the NaBen® group and 25 subjects to the placebo group. The final subject numbers in the study will depend on the sample size re-estimation after Part 1 of the study.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects who are between 12 and 17 years of age inclusive
* Physician confirmed DSM-IV or -V diagnosis of schizophrenia based on MINI International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders Studies for Children and Adolescents, version 6.0 (MINI-KID, Version 6.0)
* Are clinically stable with residual symptoms, defined as a total score of ≥ 60 of PANSS and a score of ≥ 40 for SANS
* An unchanged antipsychotic medication regimen for at least eight (8) weeks prior to randomization into the study and expected to remain unchanged during the study (longer for depot or long-acting antipsychotics: ten (10) months for Aripiprazole (Maintena®) and Paliperidone (Xeplion®); six (6) months for Olanzapine pamoate monohydrate (Zypadhera®); and at least 6 times duration of the reported half life or minimum four (4) months for other depot or long-acting antipsychotics)
* In good general physical health and all physical exam, neurological exam and laboratory assessments (urine/blood routine, biochemical tests and ECG) are clinically unremarkable per the investigator
* Subject has a negative urine illicit drug screening test
* Subject understands and is willing to sign the Informed Assent Form (IAF) prior to study entry and agrees to be available for all the study visits
* The subject's guardian understands and is willing to sign the Informed Consent Form (ICF) prior to study entry and agrees to be available for all the study visits
* Must not be a danger to self or others and must have family support available to be maintained as outpatients

Exclusion Criteria:

* Meets the DSM-IV or -V criteria at screening for mental retardation, dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, or primary substance induced psychotic disorder. Other comorbid disorders; e.g., attention-deficit hyperactivity disorder (ADHD), are allowed as long as schizophrenia is the primary diagnosis and the comorbid disorder(s) do not require medication.
* Subjects whose illness was resistant to antipsychotics according to prior trials of two different antipsychotics of adequate dose
* History of epilepsy, head trauma, or neurological illness other than Tourette's syndrome
* History of allergic reaction to sodium benzoate
* Serious medical illnesses such as acute or chronic renal disease, liver failure or heart disease that, in the opinion of the investigator, may interfere with the conduct of the study.
* Current substance abuse or positive urine illicit drug screening or history of substance dependence (including alcohol, but excluding nicotine and caffeine) in the past three (3) months.
* Use of depot antipsychotics in the past six (6) months
* Inability to follow protocol
* Body Mass Index (BMI) \> 35
* Female subjects who are pregnant (as confirmed by urine pregnancy test performed at screening Visit) or are nursing, or who do not agree to abstinence or birth control during the study
* Cancer within the last three (3) years except for basal cell carcinoma and squamous cell carcinoma
* Previous participation in an intervention trial within 30 days of randomization
* Subjects whose PANSS score has decreased more than 10 percent during the Screening Phase

Primary outcomes:
measure: Mean change from baseline in Positive and Negative Syndrome Scale (PANSS) total score after 6 weeks of treatment
timeFrame: Positive and Negative Syndrome Scale will be assessed at Visit 1 (Screening), Visit 3, 4, 5, and 6.
Secondary outcomes:
measure: Percent change from baseline in Positive and Negative Syndrome Scale (PANSS) total score from baseline after 6 weeks of treatment
timeFrame: Positive and Negative Syndrome Scale will be assessed at Visit 1 (Screening), Visit 3, 4, 5, and 6.
measure: Percentage of subjects with 20% or more reduction in Positive and Negative Syndrome Scale (PANSS) total score from baseline after six (6) weeks of treatment
timeFrame: Positive and Negative Syndrome Scale will be assessed at Visit 1 (Screening), Visit 3, 4, 5, and 6
measure: Percent change in Positive and Negative Syndrome Scale (PANSS) sub-scales
timeFrame: Positive and Negative Syndrome Scale will be assessed at Visit 1 (Screening), Visit 3, 4, 5, and 6.
measure: Percent change in Scale for Assessment of Negative Symptoms (SANS) total scores
timeFrame: Scale for Assessment of Negative Symptoms will be assessed at Visit 1 (Screening), Visit 3,4,5, and 6
measure: Percent change in Scale for Assessment of Negative Symptoms (SANS) sub-scale scores
timeFrame: Scale for Assessment of Negative Symptoms will be assessed at Visit 1 (Screening), Visit 3,4,5, and 6
measure: Percent change from baseline in the PANSS total score after 6 weeks of treatment
timeFrame: Positive and Negative Syndrome Scale will be assessed at Visit 1 (Screening), Visit 3, 4, 5, and 6
Other outcomes:
measure: Percent change in Children's Global Assessment Scale (CGAS)
timeFrame: Children's Global Assessment Scale will be assessed at Visit 1(Screening), Visit 3, 4, 5, and 6
measure: Percent change in Clinical Global Impression-Severity (CGI-S)
timeFrame: Clinical Global Impression will be assessed at Visit 1 (Screening), Visit 3, 4, 5, and 6
measure: Percent change in Children's Depression Rating Scale-Revised (CDRS-R)
timeFrame: Children's Depression Rating Scale will be assessed at Visit 1 (Screening), Visit 3, 4, 5, and 6
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Bellflower
country: United States
facility: CiTrials
state: California
city: Long Beach
country: United States
facility: Renew Behavioral Health, Inc.
state: California
city: Riverside
country: United States
facility: CiTrials
state: California
city: Hartford
country: United States
facility: Institute of Living/Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Miami
country: United States
facility: Premier Clinical Research Institute
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Baltimore
country: United States
facility: John Hopkins University - Hugo W Moser Research Institute at Kennedy Krieger Inc.
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Medical School - Psychiatry Department
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Clinical Research Institute
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center - Department of Psychiatry
state: Minnesota
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati - Dept. of Psychiatry and Behavioral Neuroscience
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: San Antonio
country: United States
facility: Focus and Balance LLC
state: Texas
city: Bothell
country: United States
facility: Pacific Institute of Medical Sciences
state: Washington
city: Richland
country: United States
facility: Zain Research, LLC
state: Washington
city: New Taipei City
country: Taiwan
facility: Chang Gung Memorial Hospital (Linkou)
city: Taipei
country: Taiwan
facility: Chang Gung Memorial Hospital (Taipei)
city: Taipei
country: Taiwan
facility: Veteran General Hospital Taipei
Study officials:
affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
name: Robert Findling, MD
role: PRINCIPAL_INVESTIGATOR
References: