Eltoprazine for the Treatment of Cognitive Dysfunction Assoc. With Schizophrenia

DESCRIPTION (provided by applicant): Schizophrenia is a common and highly disabling psychiatric disorder with a population prevalence around 1%. The manifestations of schizophrenia fall into three major domains: 1) positive symptoms; 2) negative symptoms: and 3) cognitive dysfunction. All marketed therapies for the treatment of Schizophrenia are antagonists or partial agonists of the D2 dopamine receptor which exert their effects primarily on the positive symptoms with little or no effect on negative symptoms or cognitive dysfunction. PsychoGenics proposes to study the effects of a selective 5-HT1A/1B receptor partial agonist, eltoprazine, as an adjunctive treatment for cognitive impairment associated with prefrontal dysfunction in a double-blind, placebo-controlled, parallel study comparing the effects of eltoprazine at 5mg BID to placebo as an adjunct to standard antipsychotic treatment over an eight week period. The aims of this study are: 1. Assess whether eltoprazine can improve cognitive impairmentassociated with schizophrenia on a summary score across all 7 cognitive domains from the MATRICS test battery administered at baseline, 4 weeks and 8 weeks, CPT-AX and 2-Back measures of attention and working memory. 2. Determine whether eltoprazine hasan effect on positive, negative or affective symptoms by administering the Brief Psychiatric Rating Scale (BPRS) for positive symptoms, Calgary Depression Scale (CDS) for depression, Scale for Assessment of Negative Symptoms (SANS) for negative symptoms. 3. Assess the safety of eltoprazine in a schizophrenic population and determine if there are any drug interaction effects by administering the Simpson-Angus Extrapyramidal Rating Scale (SAS), vital signs including 12 lead EEG and other laboratory measures. PUBLIC HEALTH RELEVANCE: Schizophrenia is a common and highly disabling psychiatric disorder with a population prevalence around 1%. The manifestations of schizophrenia fall into three major domains: 1) positive symptoms; 2) negative symptoms: and 3) cognitive dysfunction. All marketed therapies for the treatment of Schizophrenia are antagonists or partial agonists of the D2 dopamine receptor which exert their effects primarily on the positive symptoms with little or no effect on negative symptoms or cognitive dysfunction. PsychoGenics proposes to study the effects of a selective 5-HT1A/1B receptor partial agonist, eltoprazine, as an adjunctive treatment for cognitive impairment associated with prefrontal dysfunction in a double-blind, placebo-controlled, parallel study comparing the effects of eltoprazine at 5mg BID to placebo as an adjunct to standard antipsychotic treatment over an eight week period.