Safety and Cognitive Function Study of EVP-6124 in Patients With Schizophrenia

A Randomized Double-Blind Placebo-Controlled 12-Week Phase 2 Study of Two Different Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist(EVP-6124)or Placebo in Schizophrenia Subjects on Chronic Stable Atypical Anti-Psychotic Therapy

This study is being conducted to determine the safety and effect on cognitive function of two different doses of an investigational medication, EVP-6124, in individuals with schizophrenia who are on chronic stable atypical anti-psychotic therapy. In addition, behavioral and psychotic symptoms will be evaluated.

This is a randomized, double-blind, placebo-controlled, Phase 2 safety/efficacy study in which two dose levels of EVP-6124 will be evaluated. Eligible for enrollment will be patients who meet clinical criteria for schizophrenia and who are taking chronic atypical anti-psychotic medication at a stable dose. This study will therefore evaluate the effects of EVP-6124 when administered concomitantly with anti-psychotic medication.

Patients will be randomized to one of the following groups: 0.3 mg or 1.0 mg EVP-6124, or placebo. Seventy-five patients per group. Study drug will be supplied as capsules and will be orally administered once daily for a total of 84 days.

Inclusion Criteria:

• Subjects who meet clinical criteria for schizophrenia or schizo-affective disorder utilizing the structured clinical interview (SCI)
• Must be treated with a second generation anti-psychotic drug other than clozapine at a stable dose for at least 4 weeks and must have been on that drug and clinically stable for at least 8 weeks
• Must have no more than "moderate" severity rating for negative symptoms: BPRS item ≤4
• A minimal level of extrapyramidal symptoms (EPS); Simpson-Angus Scale total score ≤6
• A minimal level of depression; Calgary Depression Scale total score ≤10
• Must have a general health status acceptable for participation in a 12-week clinical trial
• Fluency (oral and written) in the language in which the standardized tests will be administered
• If a smoker, the ability to refrain from smoking for at least 30 minutes prior to any cognitive testing

Exclusion Criteria:

General

• Insufficiently controlled diabetes mellitus in the judgment of the investigator
• Malignant tumor within the last 5 years with the exception of squamous and basal cell carcinoma or cervical carcinoma it situ
• Pregnancy, nursing, (or if fertile female) not willing to utilize birth control measures during study
• Unstable medical condition that is clinically significant in the judgment of the investigator: major organ system dysfunction