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

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 patients. Participants will be randomly assigned to
one of treatment sequences—which will remain undisclosed to the patient 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-centre 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.

Inclusion Criteria:

1. In the opinion of the investigator, participant is capable of understanding and
complying with protocol requirements.

2. 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.

3. Is a healthy adult male.

4. Speaks English as their first language.

5. Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of
study drug.

6. Weighs at least 50 kg and has a body mass index (BMI) between 18 and 32 kg/m^2,
inclusive at Screening.

7. 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.

8. Has a normal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG)
measurement at Screening.

Exclusion Criteria:

1. Has received any investigational compound or ketamine within 30 days prior to Day 1
of Period 1.

2. Has received TAK-063 in a previous clinical study or as a therapeutic agent.

3. Is an immediate family member, study site employee, or in a dependant relationship
with a study site employee who is involved in the conduct of this study (eg, spouse,
parent, child, sibling) or may consent under duress.

4. 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.

5. Has a known hypersensitivity to any component of the formulation of TAK-063 or
ketamine.

6. Has a contraindication for ketamine.

7. Has a positive result for drugs or alcohol at Screening or Check-in (Day -1 of Period
1).

8. 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.

9. Has taken any excluded medication, supplements, or food products listed in the
Excluded Medications and Dietary Products.

10. 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.

11. 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 [eg,
cholecystectomy]).

12. 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.

13. 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.

14. 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).

15. Has poor peripheral arterial/venous access or recent wrist trauma.

16. 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.

17. 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).

18. 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).

19. Has a QT interval with Fridericia correction method (QTcF) >430 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).

20. 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).

21. 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.

22. Has a history of head injury or trauma.

23. Has any condition that would prevent an MRI from accurately or safely being performed
(eg, claustrophobia, cardiac pacemaker, metallic implants or clips), as verified per
study site's standard MRI assessment questionnaire.

24. Has a risk of suicide according to the Investigator's clinical judgment (eg, per
Columbia-Suicide Severity Rating Scale [C-SSRS]) or has made a suicide attempt in the
previous 6 months prior to Screening.