Last updated on May 2018

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


Brief description of study

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.

Detailed Study Description

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.

Clinical Study Identifier: NCT03094429

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