Schizophrenia
Conditions
Brief summary
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
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.
Interventions
DRUGSLV354
One dose of ABT-354
Sponsors
Abbott
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male, age between 18 and 55 years, inclusive. 2. Body Mass Index 18 to 30 (healthy) and 18 to 38 (schizophrenia). 3. A condition of general good physical health. 4. Schizophrenia subjects must have a diagnosis of schizophrenia based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR). 5. Schizophrenia subjects must be on a stable dose of an atypical antipsychotic for at least 4 weeks prior to Screening.
Exclusion criteria
1. Presence of a metal implant that would preclude a Magnetic Resonance Imaging (MRI) scan. 2. Radiation exposure for research purposes within the past year that will exclude participation in the study. 3. Significant current suicidal ideation within the past month as evidenced by Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening. 4. History of psychiatric diseases or disorders (healthy subjects) 5. Unsuitable to receive SLV354 or the radiotracer, \[11C\]-QUICS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain receptor occupancy | Study Day -1 | 5-HT6 receptor occupancy and the relationship between SLV354 plasma concentrations and receptor occupancy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile | Up through Study Day 4 | 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) |
Countries
United States
Outcome results
None listed