This is an adaptive, Phase II/III study in 2 parts (i.e. Part 1 (dose ranging) and Part 2 (Hypothesis testing)). NaBen® is granted Breakthrough Therapy Designation by US FDA as treatment for refractory schizophrenia.
Part 1 Objectives: There are two primary objectives for Part 1 of this study:
1. To evaluate, in terms of dose-response, the effectiveness of NaBen® (1000 and 2000 mg/day) compared to Placebo (0 mg/day), when combined with clozapine, in improving the residual symptoms associated with refractory schizophrenia in adults, and; to determine the optimal dose to be used in Part 2 of this study. 2. Sample size re-assessment to evaluate the final sample size needed to proceed with Part 2 of the study The secondary objective of the Part 1 of this study is to evaluate the safety and tolerability of NaBen® (1000 and 2000 mg/day) compared to Placebo (0 mg/day), in combination with clozapine.
Part 2 Objectives: The primary objective of the Part 2 of this study is to evaluate the effectiveness of NaBen® (at the optimal dose determined in the Part 1 of this study) compared to Placebo (0 mg/day), when combined with clozapine, in improving the residual symptoms associated with refractory schizophrenia in adults. The secondary objective of the Part 2 of this study is to evaluate the safety and tolerability of NaBen® (at the optimal dose determined in the Part 1 of this study) compared to Placebo (0 mg/day), in combination with clozapine.
Male or female subjects who are between 18 and 55 years of age inclusive
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
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
The subject has Physician confirmed DSM-V diagnosis of schizophrenia for the past 2 years based on subject's recorded history and confirmed by psychiatric evaluation and MINI International Neuropsychiatric Interview For Schizophrenia and Psychotic Disorders, version 7.0 (MINI, Version 7.0)
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
Initiation or dose change of lithium, antidepressant or other mood stabilizers within 16 weeks prior to Screening
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
The subject has previously received NaBen®
Parallel
NaBen®
Drug2000 mg/day or 1000 mg/day, twice daily
Placebo
Other intervention0 mg total, twice daily
Mean change from baseline in Positive and Negative Syndrome Scale (PANSS) total score
Mean change from baseline in Positive and Negative Syndrome Scale (PANSS) total score
Percent change from baseline in Positive and Negative Syndrome Scale (PANSS) total score
Percent change from baseline in PANSS total score treatment
Percentage of subjects with 20% or more reduction from baseline in Positive and Negative Syndrome Scale (PANSS) total score
Percentage of subjects with 20% or more reduction from baseline in PANSS total score after treatment
Percent change in PANSS sub-scales and Marder PANSS factor scores
Percent change in PANSS sub-scales and Marder PANSS factor scores
Percent change in Personal and Social Performance (PSP) scale
Percent change in Personal and Social Performance (PSP) scale
Incidence of Treatment-Emergent Adverse Events (TEAE) and incidence of withdrawals from the study due to TEAEs
Incidence of TEAE and incidence of withdrawals from the study due to TEAEs
Percent change in Simpson-Angus extrapyramidal side effects Scale (SAS)
Percent change in Simpson-Angus extrapyramidal side effects Scale (SAS)
Percent change in Abnormal Involuntary Movement Scale (AIMS)
Percent change in Abnormal Involuntary Movement Scale (AIMS)
Percent change in Barnes Akathisia Rating Scale (BARS)
Percent change in Barnes Akathisia Rating Scale (BARS)
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SyneuRx International (Taiwan) Corp
Lead sponsor
Amarex Clinical Research
Collaborator
