A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of TAK-828 Escalating Multiple-Doses in Healthy Participants

The drug being tested in this study is called TAK-828. TAK-828 is being tested to evaluate
the safety, tolerability, pharmacokinetics and pharmacodynamics in healthy non-Japanese and
Japanese participants in Parts 1 and 2, respectively.

The study will enroll approximately 56 participants. Participants will be randomly assigned
(by chance, like flipping a coin) to receive either TAK-828 or matching placebo. This
assignment will remain undisclosed to the participant and study doctor during the study
(unless there is an urgent medical need).

Proposed doses:

- Part 1: TAK-828 15 mg, 45 mg, 75 mg, 100 mg, and placebo BID

- Part 2: TAK-828 45 mg, and 100 mg, and placebo BID

All participants will be asked to take the solution at the same time each day throughout the
study.

This multi-center trial will be conducted in the United States.

Inclusion:

For Parts 1 and 2, subject eligibility is determined according to the following criteria
prior to entry into the study:

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

2. The subject or, when applicable, the subject'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 including requesting
that a subject fast for any laboratory evaluations.

3. The subject is a healthy male, or a healthy female not of child-bearing potential.
Females not of childbearing potential are defined as those who have been surgically
sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are
postmenopausal (example, defined as at least 1 year since last regular menses, with a
follicle-stimulating hormone [FSH] level of >40 international units per liter [IU/L]
or at least 5 years since last regular menses confirmed before any study drug is
administered).

4. For Part 1: the subject is a non-Japanese adult, aged 18 to 55 years (inclusive) at
the time of informed consent and first dose of study drug.

5. For Part 1: the subject weighs at least 50 kg and has a body mass index (BMI) of 18
to 30 kilogram per square meter (kg/m^2) (inclusive) at Screening.

6. For Part 2: the subject is of Japanese descent (born to Japanese parents and
grandparents), aged 20 to 55 years (inclusive) at the time of informed consent and
first dose of study drug.

7. For Part 2: the subject weighs at least 45 kilogram (kg) and has a BMI of 18.5 to 25
kg/m^2 (inclusive) at Screening.

Exclusion Criteria

For Parts 1 and 2, any subject who meets any of the following criteria will not qualify
for entry into the study:

1. The subject received any investigational compound within 30 days or 5 half-lives
(whichever is longer) before the first dose of study drug.

2. The subject used prescription or nonprescription drugs and dietary supplements within
7 days or 5 half-lives (whichever is longer) before Check-in (Day -1). Herbal
supplements and hormone replacement therapy (HRT) must be discontinued 28 days prior
to Check-in (Day -1). As an exception, acetaminophen may be used at doses of less
than or equal to (<=) 1 gram/day. Limited use of nonprescription medications that are
not believed to affect subject safety or the overall results of the study may be
permitted on a case-by-case basis following approval by the sponsor.

3. The subject is an immediate family member or 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.

4. The subject has a history or presence of any disease or condition (or there is any
finding upon review of the subject's medical history, physical examination, or
clinical laboratory tests giving reasonable suspicion of a disease) that could
interfere with study participation or safety, contraindicate taking TAK-828 or a
similar drug in the same class, or potentially confound the study results (example,
history or presence of clinically significant neurologic, cardiovascular, pulmonary,
hepatic, hematologic, renal, immunologic, metabolic, musculoskeletal,
gastrointestinal, endocrine, or psychiatric disease). It is the responsibility of the
investigator to assess the clinical significance; however, consultation with the
Takeda medical monitor may be warranted.

5. The subject has a known hypersensitivity to any component of the formulation of
TAK-828.

6. The subject has an active infection at Screening.

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

8. The subject has a history of drug abuse (defined as any illicit drug use) or a
history of alcohol abuse within 1 year, or the subject drinks 7 or more drinks/week
for females or 14 or more drinks/week for males (1 drink=5 ounces [150 milliliter
{mL}] of wine, 12 ounces [360 mL] of beer, or 1.5 ounces [45 mL] of hard liquor)
within 6 months before the Screening visit or is unwilling to abstain from alcohol
and drugs throughout the study.

9. The subject is taking or took any excluded medication, supplements, or food products
during the time periods listed in the Prohibited Medications, Foods, and Products
table

10. If male, the subject intends to donate sperm during the course of this study or for
14 weeks after the last dose of study drug.

11. The subject has any condition possibly affecting drug absorption (example,
gastrectomy).

12. The subject has a history of cancer, except basal cell carcinoma that has been in
remission for at least 5 years before Screening.

13. The subject has a positive test result for hepatitis B surface antigen (HBsAg) or
hepatitis C virus (HCV) antibody at Screening or has a known history of human
immunodeficiency virus (HIV) infection.

14. The subject 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) or cotinine test is positive at Screening or
Check-in (Day -1).

15. The subject has poor peripheral venous access.

16. The subject donated or lost 450 mL or more of his or her blood volume (including
plasmapheresis) or had a transfusion of any blood product within 30 days prior to Day
1.

17. The subject has a Screening or Check-in (Day -1) abnormal (clinically significant)
ECG. Entry of any subject with an abnormal (not clinically significant) ECG must be
approved, and documented by signature of the principal investigator or medically
qualified subinvestigator.

18. The subject has abnormal Screening or Day -1 laboratory values that suggest a
clinically significant underlying disease or the subject has the following laboratory
abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
greater than (>) 3 times the upper limit of normal (ULN).

19. The subject has a creatine kinase isoenzyme MB (CK-MB) or cardiac troponin above the
ULN at Screening or Day -1.

20. If female, the subject is of childbearing potential (example, premenopausal, not
sterilized).