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

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: SLV354

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8048
      • Site Reference ID/Investigator# 52162

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (healthy), Group 2 (schizophrenia)	Drug: SLV354; One dose of ABT-354; Other Names: ABT-354

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Earle Bain, MD, Abbott

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 15, 2011
• First Submitted That Met QC Criteria: March 1, 2012
• First Posted (Estimate): March 6, 2012

Study Record Updates

• Last Update Posted (Estimate): September 18, 2012
• Last Update Submitted That Met QC Criteria: September 14, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: M12-700