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Study to Evaluate Safety & Efficacy of NaBen® as Add-on Treatment for Schizophrenia in Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02261519
Recruitment Status : Recruiting
First Posted : October 10, 2014
Last Update Posted : September 13, 2021
Sponsor:
Information provided by (Responsible Party):
SyneuRx International (Taiwan) Corp

Tracking Information
First Submitted Date  ICMJE September 25, 2014
First Posted Date  ICMJE October 10, 2014
Last Update Posted Date September 13, 2021
Actual Study Start Date  ICMJE March 29, 2017
Estimated Primary Completion Date September 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 19, 2017)
Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 8 weeks after randomized treatment ]
Mean change from baseline in PANSS total score
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
  • Incidence of treatment-emergent adverse events and other parameters (see description for details) as measures of safety and tolerability [ Time Frame: 45 weeks ]
    The primary safety objective of this study is to evaluate NaBen® (sodium benzoate) (1000 mg/day) in terms of safety and tolerability, as measured by Incidence of treatment-emergent adverse events, Simpson-Angus extrapyramidal side effects, change in abnormal involuntary movement scale, change in Barnes Akathisia rating scale, assessment of suicidality pre C-SSRS, shift in laboratory measurements, vital signs, weight, and ECG parameters.
  • Improvement of negative symptoms of schizophrenia measured by change from baseline in PANSS negative factor score as a measure of efficacy [ Time Frame: 9 weeks after Day 0 ]
    The primary efficacy objective of this study is to evaluate the effectiveness of NaBen® (sodium benzoate) (1000 mg/day) compared to Placebo (0 mg/day) in improving the negative symptoms associated with schizophrenia in adults. This outcome will be measured as the mean change from baseline in Positive and Negative Syndrome Scale (PANSS) negative factor score after 9 weeks of randomized treatment using Sequential Parallel Comparison Design (SPCD)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2017)
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 8 weeks after treatment ]
    Percent change from baseline in PANSS total score
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 8 weeks after treatment ]
    Percentage of subjects with 20% or more reduction from baseline in PANSS total score
  • PANSS sub-scale scores and Marder PANSS factor scores [ Time Frame: 8 weeks after treatment ]
    Percent change in PANSS sub-scale scores and Marder PANSS factor scores
  • Personal and Social Performance (PSP) scale [ Time Frame: 8 weeks after treatment ]
    Percent change of Personal and Social Performance (PSP) scale
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
  • Percent change from baseline in PANSS negative factor score after 9 weeks of treatment [ Time Frame: 9 weeks from Day 0 ]
  • Percentage of subjects with 20% or more reduction from baseline in PANSS negative factor score after 9 weeks of treatment [ Time Frame: 9 weeks after Day 0 ]
  • Percent change in PANSS total and other PANSS factor scores after 9 weeks of treatment [ Time Frame: 9 weeks from Day 0 ]
Current Other Pre-specified Outcome Measures
 (submitted: March 19, 2017)
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 64 weeks ]
    Maintenance of treatment effect for PANSS total score
  • Personal and Social Performance (PSP) scale [ Time Frame: 64 weeks ]
    Maintenance of treatment effect in PSP scale
  • Schizophrenia Quality of Life Scale (SQLS) [ Time Frame: 64 weeks ]
    Percent change and maintenance of treatment effect in Schizophrenia Quality of Life Scale (SQLS)
  • Clinical Global Impression-Severity (CGI-S) and -improvement (CGI-I) [ Time Frame: 64 weeks ]
    Percent change and maintenance of treatment effect in Clinical Global Impression-Severity (CGI-S) and -improvement (CGI-I) for both overall and negative symptoms
  • Hamilton Depression Rating Scale (HDRS) [ Time Frame: 64 weeks ]
    Percent change in Hamilton Depression Rating Scale (HDRS)
  • Serum analysis [ Time Frame: 12 weeks ]
    Serum pharmacokinetic evaluations, DNA evaluations and neurotransmitter markers evaluations
  • Treatment-Emergent Adverse Events (TEAE) [ Time Frame: 64 weeks ]
    Incidence of TEAE and incidence of withdrawals from the study due to TEAEs
  • Simpson-Angus extrapyramidal side effects (SAS) scale [ Time Frame: 64 weeks ]
    Percent change in Simpson-Angus extrapyramidal side effects (SAS) scale
  • Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: 64 weeks ]
    Percent change in Abnormal Involuntary Movement Scale (AIMS)
  • Barnes Akathisia Rating Scale (BARS) [ Time Frame: 64 weeks ]
    Percent change in Barnes Akathisia Rating Scale (BARS)
  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 64 weeks ]
    Assessment of suicidality per the Columbia-Suicide Severity Rating Scale (C-SSRS)
  • Laboratory measurements (e.g., Hematology, Biochemistry, Urine analysis) [ Time Frame: 64 weeks ]
    Changes and shifts in laboratory measurements (e.g., Hematology, Biochemistry, Urine analysis) over time
  • Vital signs (e.g., Body temperature, Heart rate, Respiration rate, Blood pressure) [ Time Frame: 64 weeks ]
    Changes in vital signs (e.g., Body temperature, Heart rate, Respiration rate, Blood pressure) over time
  • Weight (e.g., BMI in kg/m2) [ Time Frame: 64 weeks ]
    Changes in weight (e.g., BMI in kg/m2)over time
  • Electrocardiogram (ECG) parameters [ Time Frame: 64 weeks ]
    Changes in Electrocardiogram (ECG) parameters over time
Original Other Pre-specified Outcome Measures
 (submitted: October 6, 2014)
  • Maintenance of treatment effect for PANSS negative factor score [ Time Frame: 45 weeks ]
  • Percent change and maintenance of treatment effect in Global Assessment of Function (GAF) [ Time Frame: 45 weeks ]
  • Percent change and maintenance of treatment effect in Schizophrenia Quality of Life Scale (SQLS) [ Time Frame: 45 weeks ]
  • Percent change and maintenance of treatment effect in Clinical Global Impression-Severity (CGI-S) and -improvement (CGI-I) for both overall and negative symptoms [ Time Frame: 45 weeks ]
  • Percent change in Hamilton Depression Rating Scale (HDRS) [ Time Frame: 45 weeks ]
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Safety & Efficacy of NaBen® as Add-on Treatment for Schizophrenia in Adults
Official Title  ICMJE An Adaptive, Phase IIb/III, Multi-center, Prospective, Randomized, Double-Blind Placebo-controlled Study of the Safety and Efficacy of NaBen® (DAAO Inhibitor), as an Add-on Treatment for Schizophrenia in Adults
Brief Summary The proposed Phase IIb/III study is designed to evaluate the safety and efficacy of NaBen® in improving the symptoms of schizophrenia in adults. NaBen® is granted Breakthrough Therapy Designation by US FDA as add-on treatment for schizophrenia. The trial is designed as a multi-center, prospective, randomized, placebo-controlled, in which adult subjects with schizophrenia will be enrolled. The study will include four parts: a 2 week Screening part, a 4 week run-in part, an 8 week double-blind treatment part, and a 52 week Open-Label Extension part.
Detailed Description

This is an adaptive, phase IIb/III, multi-center, prospective, randomized, placebo-controlled study, in which adult subjects with schizophrenia will be enrolled. The study will include four parts: a 2 week Screening part, a 4 week run-in part, and 8 week double-blind treatment part, and a 52 week Open-Label Extension part.

Screening part of the study:

The subjects will be evaluated for eligibility during the Screening part of the study.

Enrichment run-in part of the study:

Subjects who are determined to be eligible will enter the Run-in part of the study. A total of 348 Subjects will be randomized. The randomized subjects will receive 4 weeks of NaBen® or Placebo accordingly. The subjects who have completed 4 weeks of randomized treatment in both groups (NaBen® or Placebo) will be assessed and categorized intoresponders and non-responders, based on 20% or more reduction from baseline in their PANSS total scores as per the evaluations at Visit 2 and Visit 4.

Double-Blind treatment part of the study :

  • Subjects who have successfully completed the Enrichment Run-in part will enter the Double- Blind treatment part of the study per below: NaBen® treated subjects: Subjects will continue receiving NaBen® for another 8 weeks.
  • Placebo treated subjects:

    • Placebo Responders: Subjects will continue receiving Placebo for another 8 weeks.
    • Placebo Non-responders: Subjects will be re-randomized to receive NaBen® or Placebo in a 1:1 ratio for another 8 weeks.

Open-Label Extension part of the study:

All subjects who have completed the Double-Blind part of the study will continue with the Open-Label Extension part of the study to receive NaBen® for an additional 52 weeks, plus a 2 week follow-up.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Schizophrenia
Intervention  ICMJE
  • Drug: NaBen®
    500 mg twice daily (1000 mg total)
  • Other: Placebo
    0 mg twice daily (0 mg total)
Study Arms  ICMJE
  • Experimental: NaBen®
    NaBen® is a oral tablet (500 mg), which will be taken twice daily at a total dose of 1000 mg/day during this study.
    Intervention: Drug: NaBen®
  • Placebo Comparator: Placebo
    The control treatment is placebo.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 19, 2017)
348
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2014)
240
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date September 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male/female subjects between 18 and 45 years of age
  2. If female and not infertile (defined below), the subject must agree for the duration of the study to use one of the following forms of contraception 1) systemic hormonal treatment 2) an Intrauterine device (IUD) which was implanted at least 2 months prior to screening or 3) "double-barrier" contraception (condom, diaphragm and spermicide are each considered a barrier). Females are considered to be infertile if they are either a) surgically sterile or b) have had spontaneous amenorrhea for at least the last 2 years and at least 2 years after the onset of amenorrhea while not receiving hormone replacement therapy and had a Follicle-Stimulating Hormone (FSH) level greater than 40 mIU/mL and an estradiol level less than 30 pg/mL
  3. Subject is capable of providing informed consent and is willing to sign the ICF prior to study Screening and agrees to comply with the study protocol requirements
  4. Physician confirmed DSM-V diagnosis of schizophrenia for the past 2 years based on subject's history and confirmed by psychiatric evaluation and MINI International Neuropsychiatric Interview For Schizophrenia and Psychotic Disorders, version 7.0 (MINI, Version 7.0)
  5. The subject is outpatient with no hospitalization for worsening of schizophrenia within 3 months of the screening.If the subject is hospitalized during the study for worsening of schizophrenia symptoms the subject will be withdrawn from the study
  6. The subject's schizophrenia condition is clinically stable with residual symptoms. Residual symptoms will be defined as a total score of ≤110 and ≥ 60 of PANSS per Visit 1 evaluations
  7. An unchanged antipsychotic medication regimen for at least eight (8) weeks prior to screening into the study and expected to remain unchanged during the study (longer for depot or long-acting antipsychotics: ten (10) months for Aripiprazole and Paliperidone; six (6) months for Olanzapine pamoate monohydrate; and at least 6 times duration of the reported half life or minimum four (4) months for other depot or long-acting antipsychotics)
  8. In good general physical health and without clinically significant abnormalities in physical exam, neurological exam and laboratory assessments (urine/blood routine, biochemical tests and ECG) which would exclude the subject from the study in the opinion of the Investigator. For ALT and AST, clinically significant is defined as above twice the upper limit of normal.
  9. BMI between 17 and 35 inclusive
  10. Subject has a negative routine urine illicit drug screening test (including heroin, amphetamines (including MDMA/ecstasy), cocaine, cannabis or PCP)
  11. The subject has a caregiver or some other identified responsible person (e.g., family member, social worker, caseworker or nurse) as determined by the Investigator and per the local regulations. The identified caregiver should be considered reliable by the Investigator and per the local regulations in providing support to the subject to help ensure compliance with study treatment, study visits and protocol procedures who preferably is also able to provide input helpful for completing study rating scales
  12. The subject must not be a danger to self or others per the Investigator's judgment

Exclusion Criteria:

  1. Meets the DSM-IV or V criteria at screening for intellectual disability, dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, primary substance-induced psychotic disorder, dementia, or any other comorbid mental disorders that in the opinion of the Investigator may interfere with study conduct and results interpretation
  2. Subjects whose illness was resistant to antipsychotics according to prior trials of two different antipsychotics of adequate dose
  3. Subjects who have been previously treated with or are receiving clozapine
  4. Initiation or dose change of lithium, antidepressant or other mood stabilizers within 16 weeks prior to screening
  5. Initiation or dose change of benzodiazepines or sleep medications due to worsening of schizophrenia symptoms or medication side effects, or any other psychotropic medications within 4 weeks prior to screening
  6. The subject has previously received NaBen®
  7. History of epilepsy, major head trauma, or any neurological illness other than Tourette's syndrome which might impair the subject's cognition or psychiatric functioning per the investigator's judgment
  8. History of allergic reaction to sodium benzoate
  9. Serious medical illnesses such as end-stage renal disease, liver failure or heart failure that, in the opinion of the Investigator, may interfere with the conduct of the study
  10. Any significant gastrointestinal disorders that, in the opinion of the investigator, markedly alter the absorption, metabolism or elimination of sodium benzoate
  11. Any movement disorders with a total score higher than 6 on SAS scale, or more than 2 on any items of the AIMS scale
  12. Current substance abuse, or history of meeting criteria for moderate or severe substance abuse (including alcohol, but excluding nicotine and caffeine) in the past six (6) months prior to screening
  13. Female subjects who are pregnant (as confirmed by urine pregnancy test performed at Screening Visit) or are breast feeding
  14. History of cancer not in remission for the last 3 years except for basal cell carcinoma and squamous cell carcinoma
  15. Participation in a clinical trial within 3 months prior to screening or more than two clinical trials within 12 months
  16. Electroconvulsive Therapy within 6 months prior to screening
  17. The subject started a new non-medication treatment for schizophrenia or other psychiatric condition within the last 3 months prior to screening
  18. The subject's anti-EPS medications dose or regimen has changed within 2 weeks prior to screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yashar Salek, MD 1-301-956-2527 yashars@amarexcro.com
Contact: Felicia Yao 886-2-77422699 ext 136 felicia.yao@syneurx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02261519
Other Study ID Numbers  ICMJE SNR-04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party SyneuRx International (Taiwan) Corp
Original Responsible Party Same as current
Current Study Sponsor  ICMJE SyneuRx International (Taiwan) Corp
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account SyneuRx International (Taiwan) Corp
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP