Phase 1 TAK-041 First-in-Human Safety, Tolerability, and Pharmacokinetics Study

The drug being tested in this study is called TAK-041. TAK-041 is being tested to evaluate
its safety, tolerability, and PK of single and multiple doses in healthy participants and as
add-on therapy to antipsychotics in participants with stable schizophrenia. This study will
also assess the oral bioavailability in healthy participants administered with tablet
formulation compared to oral suspension formulation in fasted state, and effect of high-fat,
high-calorie meal on the PK of single dose of TAK-041 tablet formulation.

The study will enroll approximately 114 participants. The study is composed of 4 parts. Part
1 (single-rising dose [SRD], alternating panel design and a sequential panel design), Part 2
(multiple-rising dose [MRD], sequential panel design), Part 3 (open label parallel design),
and Part 4 (single dose cohort).

Part 1 consists of 5 cohorts, participants in Cohorts 1 and 2 will be randomly assigned (by
chance, like flipping a coin) to treatment sequences of 2 periods and for Cohorts 3 to 5
participants will be assigned to a single dose sequential-panel:

- TAK-041 5-160 mg

- Placebo (inactive) - this is a similar formulation that looks like the study drug but
has no active ingredient.

Part 2 consists of 4 cohorts, participants will be randomly assigned to one of the two
treatments:

- TAK-041

- Placebo Dose levels for Part 2 cohort 1 will be based on emerging safety/tolerability
and PK data from Part 1. The dose levels for Part 2 Cohorts 2 onwards will be based on
emerging safety/tolerability and available PK data from Part 1 and from preceding
cohorts in Part 2.

Part 3 consists of 2 cohorts, participants will be randomly assigned to one of the two
treatments under fasted state or fed state:

- TAK-041 40 mg tablet (Fasted state)

- TAK-041 40 mg tablet (Fed state)

Part 4 consists of 1 cohort, participants will be randomly assigned to one of the two
treatments:

- TAK-041

- Placebo The dose levels for Part 4 will be based upon the emerging safety/tolerability
and PK data of same dose in healthy participants from Part 2.

This single center trial will be conducted in the United States. Participants will remain
confined to the study site from check-in (Day -1) through Days 5 of each period in Part 1, on
Days -2 to 3, Days 7 to 10, Days 14 to 17, Day 21 to 24 in Part 2, on Days 1 to 3 in Part 3,
and on Days -2 to 3, Days 7 to 10, Days 14 to 17, Days 21 to 24 in Part 4. A final visit that
completes the study will occur 12 to 16 days after the last safety and PK follow-up visit in
Part 1, 2 and 4, and 18 days after dosing in Part 3.

Inclusion Criteria:

Healthy Participants and Participants with Schizophrenia:

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

2. The participant signs and dates a written, informed consent form and any required
privacy authorization prior to the initiation of any participant procedures including
requesting that a participant fast for any laboratory evaluations.

3. The participant is willing to comply with study restrictions described in the
protocol.

4. The participant is a healthy adult man or woman (of non-childbearing potential as
described in the protocol)

5. The participant is aged 18 to 55 years, inclusive, at the time of informed consent.

6. The participant weighs at least 45 kilogram (kg) (99 pound [lb]) with a body mass
index from 18 to 32 kilogram per square meter (kg/m^2) for healthy participants and up
to 40.5 kg/m^2 for participants with schizophrenia, 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 (as defined in the
protocol)from signing of informed consent throughout the duration of the study and for
145 days have elapsed since the last dose of study drug.

Participants with schizophrenia only-:

1. Is on a stable dose of an antipsychotic medication for at least 2 months as documented
by medical history and assessed by site staff.

2. Meets schizophrenia criteria as defined by the Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition (DSM-5) by the Mini International Neuropsychiatric
Interview (MINI).

3. Has Positive and Negative Syndrome Scale (PANSS) total score less than or equal to
(<=) 90 and PANSS Negative Symptom Factor Score (NSFS; Sum of PANSS N1, N2, N3, N4,
N6, G7, and G16) greater than or equal to (>=) 15 at screening and baseline (Day-1).

4. Has stable screening and baseline (Day -1) PANSS and NSFS total scores (less than [<]
20 percent (%) change).

Exclusion Criteria:

Healthy Participants:

1. The participant has received any investigational compound within 30 days prior to the
first dose of study drug, or due to the half-life of the investigational drug is
likely to still have detectable plasma levels of that compound.

2. The participant is an immediate family member, study site employee, or is in a
dependent relationship with a study site employee who is involved in the conduct of
this study (example spouse, parent, child, sibling) or may consent under duress

3. The participant has a known hypersensitivity to any component of the formulation of
TAK-041.

4. The participant has a positive urine/blood drug result for drugs of abuse (defined as
any illicit drug use) at Screening or Check-in (Day -1).

5. The participant taken any excluded medication, supplements, or food products during
the time periods listed in the protocol.

6. The participant is lactose intolerant (Part3 only).

7. If female, the participant is of childbearing potential (example, premenopausal, not
sterilized).

8. If male, the participant intends to donate sperm during the course of this study or
for 145 days have elapsed since the last dose of study drug.

9. The participant has evidence of current active cardiovascular, central nervous system,
hepatobiliary disease including history of biliary tree disorders, gallstones,
endoscopic retrograde cholangio pancreatography (ERCP), and/or cholecystectomy,
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 test results (including elevated alkaline phosphatase (ALP), elevated
bilirubin, elevated GGT, or elevated 5'-nucleotidase) that in the judgment of the
principal investigator represents a reasonable suspicion of a disease that would
contraindicate taking TAK-041, or that might interfere with the conduct of the study.
This includes, but is not limited to, peptic ulcer disease, cholestasis, seizure
disorders, and cardiac arrhythmias.

10. The participant has current or recent (within 6 months) gastrointestinal disease that
would be expected to influence the absorption of drugs (that is, a history of
malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent
[more than once per week] occurrence of heartburn, or any surgical intervention).

11. Had major surgery, or donated or lost 1 unit of blood (approximately 500 mL) within 4
weeks prior to Screening.

12. The participant has a history of cancer, except basal cell carcinoma that has been in
remission for at least 5 years prior to Day 1. Participant has a positive test result
for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody at Screening
or a known history of human immunodeficiency virus (HIV) infection.

13. The participant has used nicotine-containing products (including but not limited to
cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 21
days prior to Check-in on Day -1. Cotinine test is positive at Screening or Day -1.

14. The participant has poor peripheral venous access.

15. Had a transfusion of any blood product within 30 days prior to Day 1.

16. Participant has a Screening or Check-in abnormal (clinically significant)
electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically
significant) ECG must be approved, and documented by signature of the principal
investigator or a medically qualified sub-investigator.

17. The participant has a sustained resting heart rate outside the range 40 to 100 beats
per minute (bpm), confirmed on repeat testing within a maximum of 30 minutes, at
Screening or Check-in.

18. The participant has a QT interval with Fridericia correction method (QTcF) >450
millisecond (ms) or PR outside the range 120 to 220 ms, confirmed on repeat testing
within a maximum of 30 minutes, at the Screening Visit or Check-in.

19. The participant has abnormal Screening or Check-in laboratory values (> upper limit of
normal [ULN] for the respective serum chemistries) of alanine transaminase (ALT),
aspartate aminotransferase (AST), total bilirubin (TBILI), ALP, gamma-glutamyl
transpeptidase (GGT), 5'nucleotidase (Screening only) and/or abnormal urine
osmolality, confirmed upon repeat testing.

20. The participant has a clinically significant history of head injury or trauma
associated with loss of consciousness for >15 minutes.

21. Is considered by the investigator to be at an imminent risk of suicide injury to self,
other, property, or participants who within the past year prior to Screening have
attempted suicide. Participants having positive answer on item 4 or 5 on Columbia
Suicide Severity Rating Scale (C-SSRS) (based on the past year) prior to randomization
are excluded.

22. The participant has a history of significant skin reactions (hypersensitivity) to
adhesives, metals or plastic; this criterion applies only to participants
participating in the study of the two wearable digital devices.

Participants with schizophrenia only:

1. Has an undetectable level of baseline antipsychotic medication at Screening.

2. Has a lifetime diagnosis of schizoaffective disorder; a lifetime diagnosis of bipolar
disorder; or a lifetime diagnosis of obsessive compulsive disorder based on the Mini
International Neuropsychiatric Interview (MINI) combined with the general psychiatric
evaluation. As an exception, participants with a historical prior lifetime diagnosis
of schizoaffective disorder may be enrolled in the study with sponsor or designee
approval provided that the principal investigator can attest that the participant's
overall history and current clinical presentation and history is most consistent with
schizophrenia, not schizoaffective disorder.

3. Has a recent (within the last 6 months) diagnosis of panic disorder, depressive
episode, or other comorbid psychiatric conditions requiring clinical attention based
on the MINI for DSM-5 and the general psychiatric evaluation.

4. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
abuse (defined as 4 or more alcoholic beverages per day) within 1 year prior to the
Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout
the study.

5. Has a diagnosis of substance use disorder (with the exception of nicotine dependence)
within the preceding 6 months based on the MINI for DSM-5 and the general psychiatric
evaluation.

6. Has evidence or history of current clinically significant cardiovascular disease,
including uncontrolled hypertension (standing or supine diastolic blood pressure >90
millimeter of mercury (mm Hg) and/or standing or supine systolic blood pressure >145
mm Hg, with or without treatment), symptomatic ischemic heart disease, uncompensated
heart failure or recent (past 12 months) acute myocardial infarction or bypass
surgery. Controlled essential hypertension, non-clinically significant sinus
bradycardia and sinus tachycardia will not be considered significant medical illnesses
and would not exclude a participant from the study. Other well-controlled medical
illnesses may be permitted that do not increase hepatic risks or other safety risks to
the participant's participation in the judgement of the investigator in consultation
with the sponsor or designee.

7. Has evidence of clinically significant extrapyramidal symptoms as measured by a
Simson-Angus Scale (SAS) score >6.

8. The participant has evidence of depression as measured by a Calgary Depression Score
(CDSS) score >9.

9. Has received TAK-041 in a previous clinical study; or has previously or is currently
participating in this study; has received treatment with other experimental therapies
within the preceding 60 days or <5 half-lives prior to randomization, whichever is
longer; has participated in 2 or more clinical studies within 12 months prior to
Screening; or has participated in a clinical study for a psychiatric condition that is
exclusionary per this protocol.