The purpose of this study is to determine whether ketamine-induced brain activity changes are modulated by TAK-063 administration using neuroimaging battery tests.
The drug being tested in this study is called TAK-063. This study will look at brain activity changes and treatment of psychotic-like symptoms induced by ketamine, in people who take TAK-063. The study will enroll approximately 27 participants. Participants will be randomly assigned to one of treatment sequences-which will remain undisclosed to the participants during the study (unless there is an urgent medical need). Participants will receive the following study medications by the end of the study: * Ketamine intravenous infusion (IV) AND * Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient AND * Two doses of TAK-063 at one of three dose levels All participants will be asked to take 3 tablets and will receive a ketamine IV on the first day of 3 separate study periods. Participants will then be assessed for brain activity changes and other symptoms. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 7 weeks. Participants will make 6 visits to the clinic.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
27
Ketamine intravenous administration.
TAK-063 tablets
TAK-063 placebo-matching tablets
The Brain Institute, University of Utah
Salt Lake City, Utah, United States
Ketamine-Induced Brain Activity in Regions of Interest During Resting State
Ketamine model was used to enhance the sensitivity to detect an effect of phosphodiesterase 10a (PDE10a) inhibition by TAK-063 by ketamine using neuroimaging battery tests. Ketamine induced robust blood oxygen level-dependent(BOLD) functional magnetic resonance imaging(fMRI) response while maintaining minimal accompanying psychotomimetic symptoms. The regions of interest include:left anterior cingulate cortex,right anterior cingulate cortex,left posterior cingulate cortex,right posterior cingulate cortex,left striatum,right striatum,left amygdala,right amygdala,left substantia nigra,right substantia nigra,left thalamus,right thalamus,left ventrolateral prefrontal cortex,right ventrolateral prefrontal cortex,left dorsolateral prefrontal cortex,right dorsolateral prefrontal cortex,left hippocampus,right hippocampus,left subgenual cingulate/Ba25,right subgenual cingulate/Ba25,left paracingulate gyrus/Ba32, and right paracingulate gyrus/Ba32.
Time frame: Day 1: 4 hours post TAK-063 dose or placebo
Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I)
Time frame: Day 1: pre-dose and at multiple time points (up to 24 hours) postdose
Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I
Time frame: Day 1: pre-dose and at multiple time points (up to 24 hours) postdose
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 M-I
Time frame: Day 1: Pre-dose and at multiple time points (up to 24 hours) post-dose
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Baseline up to 14 days after last dose of study drug (Day 32)
Percentage of Participants Who Meet the Takeda Global Research and Development Center, Inc. (TGRD) Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
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The percentage of participants with any markedly abnormal standard safety laboratory values collected throughout study.
Time frame: Baseline up to 14 days after last dose of study drug (Day 32)
Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
The percentage of participants who meet markedly abnormal criteria designated by TGRD. Vital signs included oral temperature, respiration, blood pressure and pulse (beats per minute).
Time frame: Baseline up to 14 days after last dose of study drug (Day 32)
Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose
The percentage of participants who meet markedly abnormal criteria designated by TGRD measured throughout study.
Time frame: Baseline up to 14 days after last dose of study drug (Day 32)