Study of EVP-6124 (Alpha-7 nAChR) as an Adjunctive Pro-Cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy

Inclusion Criteria:

• Age 18 to 50 years of age, inclusive
• Resides in a stable living situation, according to the investigator's judgment, and must have an identified informant who should be consistent throughout the study. Where possible, the informant should accompany the subject at a minimum to the screening, baseline (Day 1), and final study visits and be available for telephone interview throughout the study at all visits. The informant must interact with the subject at least 2 times a week
• Diagnosis of Schizophrenia of at least 3 years duration utilizing the SCID-I, direct clinical assessments, family, informants, and past medical records
• Treated with atypical antipsychotic drug (in any approved dosage form) other than Clozapine at a stable dose for at least 8 weeks prior to screening and be clinically stable; the subject must remain clinically stable (in the opinion of the principal investigator) through randomization
• Moderate Schizophrenia clinical symptom burden as defined by the following: no more than "moderate" rating for positive symptoms (hallucinations and delusions), with a Brief Psychiatric Rating Scale (BPRS) Hallucinatory Behavior or Unusual Thought Content item score ≤ 4, and no more than a "moderate" severity rating for formal thought disorder, with a Brief Psychiatric Rating Scale (BPRS) Conceptual Disorganization item score ≤ 4
• Simpson-Angus Scale (SAS) total score ≤ 6
• Calgary Depression Scale for Schizophrenia (CDSS) total score ≤ 10
• General health status acceptable for participation in a 26-week clinical study
• Fertile, sexually active subjects (men and women) must use an effective method of contraception during the study
• Fluency (oral and written) in the language in which the standardized tests will be administered
• The ability to refrain from using any tobacco or other nicotine-containing products for at least 30 minutes before any cognitive testing

Exclusion Criteria:

• Hospitalization within 12 weeks before screening or during the screening period, or change of concomitant antipsychotic medication or dose within 8 weeks before screening or during the screening period
• Psychiatric hospitalization or incarcerations due to breakthrough symptoms or acute exacerbations for a period of 3 months before screening. Subjects with a recent "social" hospitalization or incarceration may be entered into screening after consultation with the medical monitor
• Likelihood, in the opinion of the investigator, that either the subject or informant will be unable to complete a 26-week study
• Treatment with prohibited antipsychotic drug, and/or treatment with more than 1 antipsychotic drug unless secondary antipsychotic drug is administered as an adjunctive therapy (eg, for sedation, anxiety, or insomnia), in the judgment of the investigator or medical monitor
• Current treatment with any anticholinergic agent
• Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria met for alcohol abuse within the past 3 months or substance abuse (other than nicotine) within the last 6 months before screening
• Significant suicide risk as defined by 1) suicidal ideation as endorsed on items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past year; or 2) suicidal behaviors detected by the C-SSRS during the past 2 years
• Stroke within 6 months before screening, history of brain tumor, subdural hematoma, or other clinically significant neurological condition, head trauma with loss of consciousness within 12 months before screening
• Antidepressants, unless the subject has been treated with a stable dose of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for at least 3 months before screening
• Immunosuppressants, mood stabilizers, chronic regular use of a sedative hypnotic drug, chronic intake of clinically significant doses of opioid containing analgesics or any current methadone treatment all in the judgment of the investigator may be permitted depending on the circumstance
• Use of Central Nervous System (CNS) stimulants
• Nicotine therapy (including patches), varenicline (Chantix), or similar therapeutic agent within the last six months before screening