E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment for Schizophrenia in Adults |
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E.1.1.1 | Medical condition in easily understood language |
Treatment for Schizophrenia in Adults |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the effectiveness of NaBen® (sodium benzoate) (1000 mg/day) compared to Placebo (0 mg/day), in improving symptoms associated with schizophrenia in adults. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of of the study is to evaluate the safety, tolerability and pharmacokinetics of NaBen® (sodium benzoate) (1000 mg/day), as compared to Placebo (0 mg/day) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects are required to meet all of the following criteria for randomization into the study: 1. Male or female subjects who are between 18 and 55 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, , or the subject has a Legally Authorized Representative (LAR) who can provide consent to be enrolled into the study. NOTE: If the subject’s capability to provide ongoing consent during the study alters to the degree that the subject is unable to provide ongoing consent for his/her own study participation per the Investigator and the local regulations, consent should be sought from the subject’s Legally Authorized Representative (LAR) to continue in the study. If a LAR is not available the subject will be withdrawn from the study. 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 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. Body Mass Index (BMI) between 17 and 35. 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. NOTE: The caregivers will be instructed on their responsibilities related to the study participation at the screening and consent discussions. The caregivers are expected to accompany the subject on all visits if possible. If not possible, the sites should contact the caregiver by phone at each study visit to receive any applicable inputs from him/her as well. If the designated caregiver is no longer available to participate in the study in person or by phone, another caregiver determined eligible per the Investigator and the local regulations will be considered and determined after discussion of the study responsibilities. In case no other caregiver is available the subject will be withdrawn from the study. 12. The subject must not be a danger to themself or others per the Investigator’s judgment. |
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria will be excluded from randomization into the study: 1. Meets the DSM-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 treatments of two different antipsychotics of adequate dose. 3. Subjects who have been previously treated with clozapine or are currently 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, or any other psychotropic medications due to worsening of schizophrenia symptoms or medication side effects within four (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 disorder that might affect the ratings on the EPS scales (e.g. Parkinson’s disease) or any movement disorder that is due to antipsychotic medications and is not currently controlled with anti-EPS medications 12. Current substance abuse or history of meeting criteria for moderate or severe substance abuse and/or substance dependence (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 three (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 (ECT) within six (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 (e.g. individual psychotherapy, cognitive behavioral therapy or rehabilitative therapy). 18. The subject’s anti-EPS medications dose or regimen has changed within 2 weeks prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of randomized treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 8 weeks of treatment |
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E.5.2 | Secondary end point(s) |
• Percent change from baseline in PANSS total score after 8 weeks of treatment • Percentage of subjects with 20% or more reduction from baseline in PANSS total score after 8 weeks of treatment • Percent change in PANSS sub-scales and Marder PANSS factor scores after 8 weeks of treatment Percent change of Personal and Social Performance (PSP) scale after 8 weeks of treatment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 8 weeks of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
There will be "DNA" and "SERUM BIOMARKER EVALUATIONS" per protocol. Samples will be collected for DNA testings of the study subjects. This evaluation will be used to find out more about the sub-populations who might be more responsive to the DAAO Inhibitors. for biomarkers, two groups of biomarkers (Monoamines and Amino acids) will be tested. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
this is a randomised, placebo controlled double blinded study with an open label extension |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
Germany |
Poland |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |