Clinical Trial of AVL-3288 in Schizophrenia Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Double Blind, Two Dose, Cross-over Clinical Trial of the Positive Allosteric Modulator at the alpha7 Nicotinic Cholinergic Receptor AVL-3288 in Schizophrenia Patients

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: AVL-3288
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVL-3288 10 mg<br>AVL-3288 10 mg daily for 5 days | Drug: AVL-3288<br>* daily for 5 days<br>* Other names: Anvylic-3288;|
| Experimental: AVL-3288 30 mg<br>AVL-3288 30 mg daily for 5 days | Drug: AVL-3288<br>* daily for 5 days<br>* Other names: Anvylic-3288;|
| Placebo Comparator: Placebo<br>Placebo daily for 5 days | Drug: Placebo<br>* daily for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score | Compare effect of active drug (AVL-3288) to placebo on RBANS total score | End of each 5-day treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBANS index T-score subscales | Compare effect of active drug (AVL-3288) to placebo on RBANS index T-score subscales | End of each 5-day treatment phase | 
| Brief Psychiatric Rating Scale (BPRS) Total score | Compare effect of active drug (AVL-3288) to placebo on BPRS Total Score. | End of each 5-day treatment phase | 
| Calgary Depression Rating Scale (CDRS) Total score | Compare effect of active drug (AVL-3288) to placebo on CDRS Total Score. | End of each 5-day treatment phase | 
| Scale for the Assessment of Negative Symptoms (SANS) Total score | Compare effect of active drug (AVL-3288) to placebo on SANS Total score | End of each 5-day treatment phase | 
| P50 suppression measured by electroencephalographic (EEG) | Compare P50 suppression measured by EEG between active drug (AVL-3288) and placebo | End of each 5-day treatment phase | 
| Intensity of hippocampal BOLD fMRI signal during MRI scan | Compare intensity of Hippocampal BOLD signal between active drug (AVL-3288) and placebo | end of each 5-day treatment phase |