Ketamine-Induced Brain Activity ChangesPhase 1NCT01892189

Effects of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults

A Phase 1 study testing Ketamine and TAK-063 in people with Ketamine-Induced Brain Activity Changes and Psychotic-like Symptoms, run by Takeda at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine whether ketamine-induced brain activity changes are modulated by TAK-063 administration using neuroimaging battery tests. Read more about this study

Who is it for?: Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: Ketamine-Induced Brain Activity Changes, Psychotic-like Symptoms
What is being tested?: Ketamine and TAK-063
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 27 participants
Where: 1 siteUnited States
Study dates: Aug 2013to Aug 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

In the opinion of the investigator, participant is capable of understanding and complying with protocol requirements.
The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
Is a healthy adult male.
Speaks English as their first language.
Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of study drug.
Weighs at least 50 kg and has a body mass index (BMI) between 18 and 32 kilogram per metre square (kg/m^2), inclusive at Screening.
A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
Has a normal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG) measurement at Screening.

Who cannot join

Has received any investigational compound or ketamine within 30 days prior to Day 1 of Period 1.
Has received TAK-063 in a previous clinical study or as a therapeutic agent.
Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality (including MRI or EEG), which may impact the ability of the participant to participate or potentially confound the study results.
Has a known hypersensitivity to any component of the formulation of TAK-063 or ketamine.
Has a contraindication for ketamine.

Show all 24Show fewer

Has a positive result for drugs or alcohol at Screening or Check-in (Day -1 of Period 1).
Has a history of drug or alcohol abuse or dependence (as defined by Diagnostic \& Statistical Manual of Mental Disorders, fourth Edition [DSM-IV]) within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products.
Has evidence of current cardiovascular, central nervous system (CNS), hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-063 or ketamine or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once per week] occurrence of heartburn, or any surgical intervention [e.g., cholecystectomy]).
Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1.
Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or a known history of human immunodeficiency virus infection at Screening.
Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1 of Period 1) or cotinine test is positive at Screening or Check-in (Day -1 of Period 1).
Has poor peripheral arterial/venous access or recent wrist trauma.
Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1 of Period 1.
Has a Screening and/or Check-in (Day -1 of Period 1) abnormal (clinically significant) electrocardiogram (ECG). Participant has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 50 to 90 mm Hg for diastolic, if out of range may be repeated once for eligibility determination at the Screening Visit or Check-in (Day -1 of Period 1).
Has a resting heart rate outside the range 50 to 90 beats per minute (bpm), if out of range may be repeated once for eligibility determination at the Screening Visit and/or Check-in (Day -1 of Period 1).
Has a QT interval with Fridericia correction method (QTcF) greater than (>) 430 milliseconds (ms) or PR outside the range 120 to 220 ms, if out of range may be repeated once for eligibility determination within a maximum of 5 minutes, at the Screening Visit and/or Check-in (Day -1 of Period 1).
Has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 upper limit of normal (ULN).
Has a history of Axis I/II mental disorders according to DSM-IV Axis I/II such as depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders, anorexia nervosa, bulimia nervosa, and schizophrenia.
Has a history of head injury or trauma.
Has any condition that would prevent an MRI from accurately or safely being performed (e.g., claustrophobia, cardiac pacemaker, metallic implants or clips), as verified per study site's standard MRI assessment questionnaire.
Has a risk of suicide according to the Investigator's clinical judgment (e.g., per Columbia-Suicide Severity Rating Scale [C-SSRS]) or has made a suicide attempt in the previous 6 months prior to Screening.

Trial locations and contacts

1 site in 1 country.

United States1 site

The Brain Institute, University of Utah
Salt Lake City, Utah, 84108

Other trials in United States

About this study

Official title: A Randomized, Investigator and Subject-Blind, Placebo-Controlled, Single-Dose, 3-Period, Incomplete Block Cross-Over Study to Evaluate the Effects of Single Oral Administration of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults

The purpose of this study is to determine whether ketamine-induced brain activity changes are modulated by TAK-063 administration using neuroimaging battery tests.

Read the detailed description

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.

Conditions: Ketamine-Induced Brain Activity Changes, Psychotic-like Symptoms
Being tested: Ketamine, TAK-063, TAK-063 Placebo
Keywords: Drug therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KetamineDrug
Also called Ketalar™
Ketamine intravenous administration.
TAK-063Drug
TAK-063 tablets
TAK-063 PlaceboDrug
TAK-063 placebo-matching tablets

Study groups in NCT01892189
Study group	Role	What they receive
Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg	Experimental	Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 milligram (mg), orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo	Experimental	Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg	Experimental	Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg	Experimental	Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo	Experimental	Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg	Experimental	Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg	Experimental	Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight: Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo	Experimental	Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo
Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg	Experimental	Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period Receives: Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Day 1: 4 hours post TAK-063 dose or placebo

Secondary outcomes (7)

Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I)
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
The percentage of participants with any markedly abnormal standard safety laboratory values collected throughout study.
Measured: 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).
Measured: 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.
Measured: Baseline up to 14 days after last dose of study drug (Day 32)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2013Aug 2014

First posted4 Jul 2013 (estimated)
Study startAug 2013
Primary completionAug 2014
Study completionAug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Ketamine-Induced Brain Activity ChangesStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01892189
Sponsor's protocol ID: TAK-063_102
Other IDs: U1111-1141-2177
Status last verified: Apr 2026
First submitted: 20 Jun 2013
Last updated: 8 May 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Investigator and Subject-Blind, Placebo-Controlled, Single-Dose, 3-Period, Incomplete Block Cross-Over Study to Evaluate the Effects of Single Oral Administration of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults
ClinicalTrials.gov ID: NCT01892189
Acronym / sponsor ID: TAK-063_102
Conditions: Ketamine-Induced Brain Activity Changes, Psychotic-like Symptoms
Keywords: Drug therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: Aug 2013
Primary completion: Aug 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 4 Jul 2013 (estimated)
Results: Posted 12 Jan 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine whether ketamine-induced brain activity changes are modulated by TAK-063 administration using neuroimaging battery tests.

Detailed description

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.

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 design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 9

Arm	Type	Receives
Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 milligram (mg), orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.
Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.
Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.
Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.
Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period
Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.
Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight: Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period
Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.
Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg	Experimental	Drug: Ketamine, Drug: TAK-063, Drug: TAK-063 PlaceboPeriod 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

In the opinion of the investigator, participant is capable of understanding and complying with protocol requirements.
The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
Is a healthy adult male.
Speaks English as their first language.
Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of study drug.

Key exclusion criteria (24 listed)

Has received any investigational compound or ketamine within 30 days prior to Day 1 of Period 1.
Has received TAK-063 in a previous clinical study or as a therapeutic agent.
Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality (including MRI or EEG), which may impact the ability of the participant to participate or potentially confound the study results.
Has a known hypersensitivity to any component of the formulation of TAK-063 or ketamine.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KetamineAlso: Ketalar™Ketamine intravenous administration.	Drug	Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg, Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo, Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg, Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg, Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo, Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg, Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg, Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo, Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg
TAK-063TAK-063 tablets	Drug	Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg, Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo, Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg, Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg, Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo, Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg, Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg, Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo, Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg
TAK-063 PlaceboTAK-063 placebo-matching tablets	Drug	Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg, Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo, Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg, Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg, Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo, Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg, Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg, Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo, Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg

Primary outcome

Ketamine-Induced Brain Activity in Regions of Interest During Resting State
Time frame: Day 1: 4 hours post TAK-063 dose or placebo
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.

7 secondary outcomes

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
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
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
Time frame: Baseline up to 14 days after last dose of study drug (Day 32)

Results and safety

Results posted to the registry on 12 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo + TAK-063 3 mg + TAK-063 30 mg	3	3
TAK-063 3 mg + TAK-063 30 mg + Placebo	3	3
TAK-063 30 mg + Placebo + TAK-063 3 mg	3	3
Placebo + TAK-063 3 mg + TAK-063 300 mg/10 mg	3	3
TAK-063 3 mg + TAK-063 300 mg/10 mg + Placebo	3	3
TAK-063 300 mg/10 mg + Placebo + TAK-063 3 mg	3	3
Placebo + TAK-063 30 mg + TAK-063 300 mg/10 mg	3	3
TAK-063 30 mg + TAK-063 300 mg/10 mg + Placebo	3	3
TAK-063 300 mg/10 mg + Placebo + TAK-063 30 mg	3	3

Primary outcome: Ketamine-Induced Brain Activity in Regions of Interest During Resting State

Time frame: Day 1: 4 hours post TAK-063 dose or placebo. Mean (Standard Deviation). Unit: percent signal change in brain activity

Measure	Placebo n = 22	TAK-063 3 mg n = 14	TAK-063 10 mg n = 14	TAK-063 30 mg n = 15
Left Anterior Cingulate Cortex	0.4954 (0.53382)	0.2943 (0.67925)	0.4439 (0.72261)	0.3876 (0.47127)
Right Anterior Cingulate Cortex	0.4611 (0.44870)	0.2542 (0.55542)	0.4199 (0.70069)	0.3251 (0.47592)
Left Posterior Cingulate Cortex	0.4922 (0.52563)	0.4647 (0.52746)	0.5316 (0.77685)	0.3987 (0.49018)
Right Posterior Cingulate Cortex	0.5412 (0.52336)	0.4515 (0.57054)	0.6132 (0.79296)	0.3783 (0.55473)
Left Striatum	0.2914 (0.40513)	0.0644 (0.47601)	0.3045 (0.51442)	0.2453 (0.40828)
Right Striatum	0.3605 (0.37202)	0.1154 (0.52174)	0.3124 (0.46817)	0.2617 (0.36033)
Left Amygdala	0.3413 (0.66866)	0.4776 (0.72631)	0.4888 (0.60449)	0.3435 (0.57560)
Right Amygdala	0.2102 (0.72431)	0.1180 (0.85125)	0.0106 (0.76838)	0.2686 (0.53395)

Placebo vs TAK-063 3 mg: Least Squares (LS) Mean Difference: -0.2348 (95% CI -0.6506 to 0.1809), p = 0.259, ANOVA
Placebo vs TAK-063 10 mg: LS Mean Difference: -0.0367 (95% CI -0.4853 to 0.4119), p = 0.869, ANOVA
Placebo vs TAK-063 30 mg: LS Mean Difference: -0.2180 (95% CI -0.6441 to 0.2081), p = 0.306, ANOVA

Population analysed: The pharmacodynamic (PD) analysis set included all participants in the safety set and with at least 1 valid PD assessment. PD analysis set did not include 2 participants treated with TAK-063 300 mg.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to 14 days after last dose of study drug (Day 32). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 22 (0%)	15 of 22 (68.2%)	Not reported
TAK-063 3 mg	0 of 14 (0%)	7 of 14 (50%)	Not reported
TAK-063 10 mg	0 of 14 (0%)	8 of 14 (57.1%)	Not reported
TAK-063 30 mg	0 of 15 (0%)	13 of 15 (86.7%)	Not reported
TAK-063 300 mg	0 of 2 (0%)	2 of 2 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Takeda Development Center Americas, Inc. (Note: This product was divested to Axsome in 2026)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ketamine and TAK-063 in people with Ketamine-Induced Brain Activity Changes and Psychotic-like Symptoms, run by Takeda at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ketamine-Induced Brain Activity in Regions of Interest During Resting State (time frame: Day 1: 4 hours post TAK-063 dose or placebo). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01892189.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.