An Adaptive Phase II/III, Two-Part, Double-Blind, Randomized, Placebo-controlled, Dose-Finding, Multi-center Study of the Safety and Efficacy of NaBen®, as an Add-on Therapy With Clozapine, for Residual Symptoms of Refractory Schizophrenia in Adults

This is a Phase II/III, double-blind, randomized, placebo-controlled, two-part, dose-finding, Multi-center study, in which subjects with refractory schizophrenia will be enrolled. This study will be conducted in two parts: In Part 1 (i.e. dose finding portion) of the study One hundred seventy one (171) subjects will be randomized in a 1:1:1 ratio (NaBen® 2000 mg/day: NaBen® 1000 mg/day: Placebo). All subjects, after signing the Informed Consent Form (ICF), will be assessed during the screening phase. This screening phase is designed to exclude subjects who have had more than 20 percent reduction in the PANSS total score using PANSS score evaluations at Visit 1 and Visit 2. Only those subjects who successfully complete the screening phase and still meet the study eligibility criteria will proceed with Randomization and the double-blind treatment. All randomized subjects will receive eight (8) weeks of randomized treatment (NaBen® 2000 mg/day, NaBen® 1000 mg/day or Placebo). Study treatments will be given twice daily. An Interim Analysis (IA) will be conducted when 171 subjects in Part 1 of the study have been randomized and completed 8 weeks of treatment or early terminated, whichever occurs first. Randomization of subjects in the study will continue until the IA of the Part 1 data is completed. The data from the Part 1 analysis will be reviewed by an independent Data Safety and Monitoring Committee (DSMC) who would assess the data for both safety and efficacy trends. The DSMC responsibilities will be further elaborated in the DSMC charter. The DSMC will approve continuation of the study and recommend the optimal dose and sample size adjustment for the Part 2 of the study. Assuming no sample size adjustment was made as a result of the IA, for Part 2 of the study a total of 116 subjects will be randomized in a 1:1 ratio, of which 58 subjects will be randomized to the NaBen® optimal dose group and 58 subjects to the Placebo group. The procedures and assessments for subjects in Part 1 and Part 2 of this study will be identical with the exception of the randomization schema.