Safety, Tolerability, and Pharmacokinetics of Multiple-Dose TAK-058 in Healthy Participants

The drug being tested in this study is TAK-058, which is under evaluation for the treatment
of schizophrenia.

This study will enroll approximately 32 healthy non-elderly and 8 healthy elderly
participants. Participants will be randomly assigned (by chance, like flipping a coin) to
one of the four treatment groups—which will remain undisclosed to the patient and study
doctor during the study (unless there is an urgent medical need):

- TAK-058 25 mg

- TAK-058 75 mg

- TAK-058 150 mg

- TAK-058 300 mg

- Placebo (dummy inactive solution ) - this is an oral solution that looks like the study
drug but has no active ingredient.

This single-centre trial will be conducted in the United States. The overall time to
participate in this study is 40 days if assigned to TAK-058 25mg, 75mg or 150mg dose.
Participants will be confined to the clinic for 12 days, and will be contacted by telephone
11 and 30 days after last dose of study drug for a follow-up assessment (Days 21 and 40).

The overall time to participate in this study is 32 days if assigned to Cohort 5.
Participants will be confined to the clinic for 4 days, and will be contacted by telephone
14 days after last dose of study drug for a follow-up assessment (Day 14).

Inclusion Criteria:

- Ages for this study are 18 to 60 years for non-elderly and 18 to 65 years for
elderly.

- 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.

- A female participant with no childbearing potential, which is defined as the subject
has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal
ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2
years and follicle-stimulating hormone [FSH]>40 IU/L).

- Weighs at least 45 kg (99 lbs) and has a body mass index (BMI) between 18.0 and 30.0
kg/m^2, inclusive at Screening.

Exclusion Criteria:

- Has received any investigational compound within 30 days prior to the first dose of
study medication.

- Has received TAK-058 in a previous clinical study.

- 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 (eg, spouse,
parent, child, sibling) or may consent under duress.

- Has a known hypersensitivity to any component of the formulation of TAK-058.

- Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day
-1).

- Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
abuse within 6 months prior to the Screening Visit or is unwilling to agree to
abstain from alcohol and drugs throughout the study.

- Female participants of childbearing potential (premenopausal, non-sterilized), or has
a positive pregnancy test.

- Male participants that intend to donate sperm during the course of this study or for
12 weeks thereafter.

- Has evidence of current cardiovascular, central nervous system, 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 subject's medical history, physical examination, or safety
laboratory tests giving reasonable suspicion of a disease that would contraindicate
taking TAK-058, 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 previously had a seizure or convulsion (lifetime), including absence seizure and
febrile convulsion.

- Has current or recent (within 6 months) gastrointestinal disease that would be
expected to influence the absorption of drugs (ie, a history of malabsorption, any
surgical intervention known to impact absorption [eg, bariatric surgery or bowel
resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent
[more than once per week] occurrence of heartburn).

- Has a history of cancer or other malignancy, except basal cell carcinoma that has
been in remission for at least 5 years prior to Day 1.

- Has a positive test result for hepatitis B surface antigen (HBsAg), antibody to
hepatitis C virus (anti-HCV) or a known history of human immunodeficiency virus
infection at Screening.

- Has poor peripheral venous access.

- 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 45 days prior to
Day 1.

- Has a Screening or Check-in (Day -1) abnormal (clinically significant [CS])
electrocardiogram (ECG).

- Has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 60
to 90 mm Hg for diastolic, confirmed with one repeat testing within a maximum of 5
minutes, at the Screening Visit or Check-in (Day -1) Visit.

- Has a resting heart rate outside the range 50 to 100 bpm, confirmed with repeat
testing within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1)
Visit.

- Has a QT interval with Fridericia's correction method (QTcF) >450 ms (males) or >470
ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat
testing within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1)
Visit.

- Has abnormal Screening or Check-in (Day -1) laboratory values that suggest a CS
underlying disease or subject with the following lab abnormalities: ALT and/or AST
>1.5 the upper limits of normal.

- 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.

- Has uncontrolled, CS neurologic, cardiovascular, pulmonary, hepatic, renal,
metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric
disorder, or other abnormality, which may impact the ability of the subject to
participate or potentially confound the study results.

- Has used nicotine-containing products (including but not limited to cigarettes,
electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine
gum) within 28 days prior to Check-in (Day -1). Cotinine test is positive at
Screening or Check-in (Day -1).