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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TS-134; Drug: TS-134; Other: Ketamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Taisho Pharmaceutical R&D Inc.
• Investigators: Principal Investigator: Jeffrey A Lieberman, MD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2017
• Primary Completion (Actual): April 4, 2018
• Study Completion (Actual): April 10, 2018

Study Registration Dates

• First Submitted: May 3, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 5, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2018
• Last Update Submitted That Met QC Criteria: April 27, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: fMRI; ketamine; TS-134
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: TS134-US103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No