Effects of TS-134 on Ketamine-induced BOLD Signals in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effects of TS-134 on ketamine-induced BOLD signals in ROIs in resting fMRI in healthy adult subjects.

Official Title
-----------------
A Randomized, Single-blind, Parallel-group Study to Evaluate the Effects of TS-134 on Ketamine-induced BOLD Signals in Resting fMRI in Healthy Adult Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: TS-134
* Drug: TS-134
* Drug: Placebo
* Other: Ketamine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult male and female subjects between 18 and 55 years of age inclusive (at the time of initial informed consent) Body weight ≥ 45 and ≤ 87 kg Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 Exclusion Criteria: Female subjects who are pregnant, intend to become pregnant, or are breastfeeding History or presence of psychiatric or neurologic disease or condition History of first-degree relative with schizophrenia or mood disorder with psychosis History of alcohol or drug abuse History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine History of violence Presence or positive history of significant medical illness, including high blood pressure, low blood pressure or orthostatic hypotension Any subjects who show subthreshold ketamine BOLD response Metal implants, pacemaker, other metal or paramagnetic objects contained within the body Claustrophobia Subject with any history of suicidal behavior or is currently at risk of suicide in the opinion of the investigator

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TS-134 20 mg<br> | Drug: TS-134<br>* Multiple dose titrations from 10 mg to 20 mg once daily for 6 days<br>Other: Ketamine<br>* 0.23 mg/kg bolus over one minute on Screening (baseline) and Day 6<br>|
| Experimental: TS-134 60 mg<br> | Drug: TS-134<br>* Multiple dose titrations from 10 mg to 60 mg once daily for 6 days<br>Other: Ketamine<br>* 0.23 mg/kg bolus over one minute on Screening (baseline) and Day 6<br>|
| Experimental: Placebo<br> | Drug: Placebo<br>* Multiple doses of placebo once daily for 6 days<br>Other: Ketamine<br>* 0.23 mg/kg bolus over one minute on Screening (baseline) and Day 6<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD fMRI signals in pre-specified ROIs | Changes in ketamine-induced BOLD fMRI signals in pre-specified ROIs (anterior cingulate cortex (ACC) and anterior insula) following administrations of TS-134 | Screening and Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD fMRI signals in whole brain | Changes in ketamine-induced BOLD fMRI signals in whole brain following administrations of TS-134 | Screening and Day 6 | 
| Brief Psychiatric Rating Scale (BPRS) | Changes in BPRS scores following administrations of TS-134 | Screening and Day 6 | 
| Clinician Administered Dissociative State Scale (CADSS) | Changes in CADSS scores following administrations of TS-134 | Screening and Day 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TS-134, ketamine, fMRI