A Positron Emission Tomography Study of SLV354 in Healthy Subjects and Subjects With Schizophrenia

Study Overview
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Brief Summary
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This open-label, Phase 1 study will investigate the 5-hydroxytryptamine 6 (5-HT6) receptor occupancy in the brain using positron emission tomography (PET) following single oral doses of SLV354. Up to 22 healthy male subjects and male subjects with stable schizophrenia, between 18-55 years of age are to complete the study.

Detailed Description
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This is an exploratory, open-label PET study designed to examine the relationship between SLV354 plasma concentration and 5-HT6 receptor occupancy in the brain following single oral doses of SLV354 in healthy male subjects and male subjects with stable schizophrenia. A total of up to 22 subjects are to complete the study, including approximately 12 subjects with schizophrenia on a stable dose of an atypical antipsychotic medication. Within 60 days prior to the PET scan, subjects will be screened based on medical history, physical examination, vital signs, ECG, clinical laboratory tests, response to Columbia-Suicide-Severity Rating Scale (C-SSRS) and for schizophrenia subjects only, the diagnosis of schizophrenia based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR). Following Screening, eligible subjects will have a Magnetic Resonance Imaging (MRI) scan, unless one was performed within one year of the PET scan, to delineate the region of interest for the individual PET images. The radiotracer [11C]-QUICS will be used for the PET scans. All subjects will receive a single oral dose of SLV354. Healthy subjects will have one PET scan prior to and two PET scans after administration of SLV354. Schizophrenia subjects will have two PET scans prior to and one PET scan after administration of SLV354.

Official Title
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An Open-Label, Positron Emission Tomography (PET) Study to Evaluate the Brain 5 HT6 Receptor Occupancy by Single Doses of SLV354 in Healthy Male Subjects and Subjects With Stable Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SLV354


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male, age between 18 and 55 years, inclusive. Body Mass Index 18 to 30 (healthy) and 18 to 38 (schizophrenia). A condition of general good physical health. Schizophrenia subjects must have a diagnosis of schizophrenia based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR). Schizophrenia subjects must be on a stable dose of an atypical antipsychotic for at least 4 weeks prior to Screening. Exclusion Criteria Presence of a metal implant that would preclude a Magnetic Resonance Imaging (MRI) scan. Radiation exposure for research purposes within the past year that will exclude participation in the study. Significant current suicidal ideation within the past month as evidenced by Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening. History of psychiatric diseases or disorders (healthy subjects) Unsuitable to receive SLV354 or the radiotracer, [11C]-QUICS.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (healthy), Group 2 (schizophrenia)<br> | Drug: SLV354<br>* One dose of ABT-354<br>* Other names: ABT-354;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain receptor occupancy | 5-HT6 receptor occupancy and the relationship between SLV354 plasma concentrations and receptor occupancy | Study Day -1 | 
| Brain receptor occupancy | 5-HT6 receptor occupancy and the relationship between SLV354 plasma concentrations and receptor occupancy | Study Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile | Maximum observed plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration-time curve (AUC), terminal elimination half-life (t1/2), oral plasma clearance (CL/F) | Up through Study Day 4 |