A Study to Evaluate Efficacy, Tolerability, Pharmacodynamic and Pharmacokinetics of Multiple Oral Doses of TAK-831 in Adults With Schizophrenia

The drug being tested in this study is called TAK-831. TAK-831 is being tested to treat
people with schizophrenia.

The study will enroll approximately 32 patients. Participants will be randomly assigned to
one of the two treatment sequences which will remain undisclosed to the patient and study
doctor during the study (unless there is an urgent medical need):

- TAK-831 500 mg followed by matching placebo

- Matching placebo followed by TAK-831 50 mg

The first 16 participants will receive TAK-831 500 mg during the treatment period in which
they are assigned to TAK-831. Following an interim analysis, there will be a study-wide
decision about whether to treat the additional 16 participants with TAK-831 500 mg during the
active treatment period to or treat them with TAK-831 50 mg during this period. After the
interim analysis, the participant and study doctor will not be aware of which TAK-831 dose is
being used.

This single center trial will be conducted in United States of America. The overall time to
participate in this study is approximately 81 days. Two treatment periods will be
administered for 8 consecutive days, separated by a 14 to 21-day washout. Participants will
be admitted to the clinic for two overnight stays at the beginning of each treatment period
and one night at the end of each treatment period. After the second treatment period, a final
follow-up safety assessment visit will be conducted approximately 10 to 14 days after the
last administration of study drug.

Inclusion Criteria:

- Have a body mass index (BMI) greater than or equal to (>=) 18.5 and less than or equal
to (<=) 40.0 (kilogram per square meter [kg/m^2]) at the Screening Visit.

- With a current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
(DSM-5) diagnosis of schizophrenia who are receiving stable antipsychotic therapy (no
increase, no decrease greater than [>] 20% in dose in the preceding 2 months).

- Positive and Negative Syndrome Scale (PANSS) negative symptom factor score (NSFS) >=
15, stable screening and baseline PANSS NSFS (< 25% change).

- PANSS total score <= 90; stable screening and baseline PANSS total score (less than
[<] 20% change).

- Receiving stable (no increase, no decrease > 25% in dose in the preceding 2
months)antipsychotic medication at doses not to exceed risperidone 6 mg or its
equivalent. Concomitant treatment with a subtherapeutic dose of a second antipsychotic
may be permitted with sponsor or designee approval if used as a hypnotic (maximum of
quetiapine 100 mg or its equivalent once daily at bedtime), but not if it is used for
refractory positive psychosis symptoms. Under this exception, the total daily dose the
second antipsychotic will not have to be included in the calculation of the 6 mg/day
risperidone-equivalent limit.

Exclusion Criteria:

- Has a history of cancer (malignancy) excluding treated basal cell carcinoma or treated
stage 0 (in situ) cervical carcinoma.

- Has a history of significant multiple and/or severe allergies (example [eg], food,
drug, latex allergy) or has had an anaphylactic reaction or significant intolerability
to prescription or nonprescription drugs or food.

- Has a QT interval with Fridericia's correction method (QTcF) > 450 milliseconds [ms]
(males) or > 470 ms (females) confirmed with one repeat testing, at the Screening
Visit or Check-in.

- Has a positive alcohol or drug screen for disallowed substances, including
amphetamines, barbiturates, cocaine, marijuana, methadone, methamphetamine,
3,4-methylenedioxymethamphetamine, phencyclidine, or nonprescribed benzodiazepines or
opiates.

- Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or has
HIV by history (confirmatory testing is allowed; most sensitive test should take
precedence).

- Had major surgery, donated or lost 250 milliliter [mL] of blood within 4 weeks prior
to the prestudy (screening) visit.

- Has a known hypersensitivity to any component of the formulation of TAK-831.

- Has a history of significant skin reactions (hypersensitivity) to adhesives, metals or
plastic.

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