Basmisanil Positron Emission Tomography Study in Japanese Volunteers

Study Overview
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Brief Summary
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This study will evaluate the relationship between basmisanil plasma concentrations and the occupancy of Gamma-Amino Butyric Acid A (GABAA) receptor subtypes containing an alpha5 (α5) subunit in healthy Japanese volunteers. Each participant will have two post-screening imaging sessions. In the first imaging session, participants will have a baseline Positron Emission Tomography (PET) scan. In the second imaging session, participants will receive a single oral dose of basmisanil, followed by two on-treatment PET scans at about 4 and 10 hours post-dose.

Official Title
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A Single-Centre, Non-Randomised, Open Label, Positron Emission Tomography Imaging Study to Assess Occupancy of α5-Containing GABAA Receptors by RO5186582 in Healthy Volunteers of Japanese Origin

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Basmisanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Japanese healthy volunteer, who was born in Japan, has 4 ethnically Japanese grandparents and has lived outside Japan for no longer than 5 years A body mass index (BMI, Quetelet index) in the range 18.0 to 32.0 kilograms per square meter (kg/m^2) Willingness and ability to comply with study restrictions Exclusion Criteria: A history of epilepsy, convulsions or significant head injury, or other structural brain abnormality Pregnant or lactating or not using acceptable contraception Presence or history of severe adverse reaction to any drug or a history of sensitivity to basmisanil or the PET radioligand (RO15-4513) Significant exposure to radiation within the previous 12 months Any other clinically relevant abnormalities, concomitant diseases or ongoing medical conditions

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Basmisanil in Japanese Healthy Volunteers<br>Japanese healthy volunteers will receive a single oral dose of RO5186582 within 15 minutes after completing a standard meal. | Drug: Basmisanil<br>* Single oral dose: Basmisanil doses between 20 milligrams (mg) and 960 mg may be used in this study. The planned doses for the first two participants are 160 mg and 480 mg, respectively. Basmisanil dose for subsequent participants will be decided by the investigator and sponsor during the study, based on on-going review of emerging data.<br>* Other names: RO5186582, RG1662;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Brain α5 Subunit-Containing GABAA Receptors Occupied by Basmisanil (Receptor Occupancy) Following a Single Dose of Basmisanil in Selected Regions of Interest (ROIs) Assessed by PET Imaging |  | Day 1 | 
| Correlation Between Basmisanil Plasma Concentration and Occupancy of Brain α5 Subunit-Containing GABAA Receptors |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain GABAA Receptor α5 Subunit Levels in Selected ROIs Assessed by PET Imaging |  | Day 1 | 
| Percentage of Participants With Adverse Events |  | From Baseline up to 7-14 days |