A double-blind, placebo-controlled, multicenter, parallel group study to assess efficacy, safety and tolerability of TC-5619 as augmentation therapy to improve negative symptoms and cognition in outpatients with schizophrenia

INTERVENTION: Product Name: TC‐5619 Product Code: TC‐5619‐23 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: TC‐5619‐23‐CRD‐003 CAS Number: 1111941‐90‐2 Current Sponsor code: TC‐5619‐23 Concentration unit: mg milligram(s) Concentration type: range Concentration number: 5‐25 Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Schizophrenia Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To assess the efficacy of TC‐5619 to improve negative symptoms and cognition when used as augmentation therapy to atypical antipsychotics in stable outpatients with schizophrenia ; Primary end point(s): Primary efficacy endpoint ; ‐ SANS total score, comparing TC‐5619 vs. placebo from Baseline (Day 1) to Week 24 or Early Withdrawal (EW) as a function of Treatment. Secondary Objective: 1. To assess the safety and tolerability of TC‐5619 administered adjunctively with atypical antipsychotics; 2. To assess the disposition of TC‐5619 and investigate pharmacokinetic/ pharmacodynamic (PK/PD) relationships. Timepoint(s) of evaluation of this end point: ‐ SANS Total Score ; Week ‐4, Day 1, Week 4, 8, 12, 18, 24, 26 (Follow Up) or Early Withdrawal (EW) SECONDARY OUTCOME: Secondary end point(s): Key secondary endpoints are:; ‐ The CogState Schizophrenia Battery (CSB) composite score,; ‐ University of San Diego (UCSD) Performance Based Skills Assessment, brief version (UPSA‐Brief).; ; Secondary efficacy endpoints are:; ‐ Subject Global Impression – Cognition (SGI‐Cog) scale; ; ‐ Clinical Global Impression of Severity (CGI‐S); ; ‐ Clinical Global Impression‐Global Improvement (CGI‐I); ; ‐ PANSS total score; ; ‐ Positive Symptoms score from PANSS; ; ; Other Endpoints (for tobacco users only) are: ; ‐ Tobacco use: ; ‐ Fagerström Test for Nicotine Dependence score (FTND): ; ; ‐ PK Endpoint; Timepoint(s) of evaluation of this end point: Timepoints as per protocol for various tests i.e; Week ‐4, Day 1, Week 4, Week 8, Week 12, Week 18, Week 24 or Early Withdrawal, Week 26 (Follow up); INCLUSION CRITERIA: 1. Diagnosis of schizophrenia, per Diagnostic and Statistical Manual of Disorders, Edition 4, Text Revision (DSM‐IV‐TR) criteria, as aided by the MINI International Neuropsychiatric Interview (MINI). 2. Controlled schizophrenia, on a stable dose of an approved atypical antipsychotic for at least 2 months prior to screening.Screening through Day 1. Approved refers to regulatory approval in the country of use. and as indicated in Appendix 2. 3. Age 18 – 60, male or female 4. Stable schizophrenia as documented by a lack of psychiatric hospitalization for 2 months prior to Screening through Day 1 (social admissions for the convenience of the subject allowed). 5. Clinical history of stable psychotic symptoms for 1 month prior to Screening through Day 1. 6. Stable positive symptoms of schizophrenia for 4 weeks prior to Day 1, as shown by score = 4 on the Positive and Negative Symptoms Scale (PANSS) for each of the items related to delusion, halluci