Single-center, outpatient, randomized, double-blind, placebo-controlled, 3-treatment-phase, cross-over study to evaluate the safety, tolerability and efficacy of two oral doses of AVL-3288 each compared to placebo, in patients with schizophrenia.

This study will be in 24 non-smoking outpatients with schizophrenia or schizoaffective disorder. Subjects will complete three treatment phases, each involving 5 straight days of taking AVL-3288 (10 mg or 30 mg study drug or placebo) followed by a 16 day washout period in which subjects do not take the study drug to ensure that the drug is completed eliminated from the body before the next phase.

Inclusion Criteria:

• DSM-V diagnosis of schizophrenia or schizoaffective disorder
• RBANS Total Scale Score >62
• Willing to provide informed consent
• Medically stable for study participation
• Taking an antipsychotic medication other than clozapine at a stable dose for at least 4 weeks
• Judged clinically not to be at significant suicide or violence risk

Exclusion Criteria:

• Substance abuse (excluding nicotine) within last 90 days
• ECG abnormality that is clinically significant
• Current clozapine use
• Participation in a study of investigational medication/device within 4 weeks
• Pregnancy, lactation, or lack of use of effective birth control
• Active tobacco use
• Presence or positive history of significant medical or neurological illness, including cardiac illness, WBC <3500/mm3, absolute neutrophil count <1500/mm3, ALT or AST values >1.5 times upper limit of normal. Hemoglobin less than 130 g/L (13 g/dL) in males or 120 g/L (12 g/dL) in females or known HIV +
• Contraindication to MRI scanning, including metal implants or claustrophobia
• Medicinal patch, unless removed