Study to Demonstrate Cognitive Enhancing Effects of BF2.649

We will recruit persons with schizophrenia or schizoaffective disorder who are not currently experiencing an acute exacerbation of psychotic symptoms, but still display cognitive symptoms and have consequent psychosocial dysfunction. The subjects recruited will be taking haloperidol, aripiprazole, risperidone or paliperidone. Each study subject will spend 4 weeks on a fixed dose of his or her APD with stable symptoms, during which time the baseline workup will be completed. At baseline (Week 0), each study subject will have a full symptom evaluation, side effects, and neuropsychological battery along with the full clinical laboratory and baseline safety study workup. Next, subjects, while remaining on their APD, will be randomized to BF2.649 or placebo. The dose of BF2.649 will be up to 20 mg/day. Assessment of safety parameters (vital signs, EKGs, clinical labs) and side effects (adverse events, BAS, SAS) will occur once weekly for the first 4 weeks (through study week 4) and then every other week for the next 4 weeks (to study week 8) including End of Study (week 12). An EEG will be taken at Week 1 and then at Week 8. Symptomatic outcome measures (PANSS and CGI) will be measured every two weeks during the double blind phase and at end of study. The neuropsychological battery will be done first at baseline and repeated at the end of the 8-week double blind phase. After 8 weeks of medication, the double-blinded drug will be stopped and the patient followed for a period 4 weeks with clinical and side effect measures recorded weekly with the exception of clinical laboratories, which will be recorded every other week. Each study participant will be seen weekly throughout the protocol for clinical assessment. Finally, persons with schizophrenia display severe deficits in neuropsychological, cognitive, and social functioning. Our primary outcome measure will be to determine if BF2.649 can produce a cognitive enhancing effect and repair some of the neuropsychological deficiencies seen in this population. Therefore, blood samples will be collected from study volunteers for DNA analysis, serology testing, and white cell immortalization during and only at the baseline phase of the study (Week 0). If a therapeutic effect is seen, it will be important to be able to identify the genetic characteristics of the responders to BF2.649.