A Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of 3 Dose Levels of TAK-831 in Adjunctive Treatment of Adult Participants With Negative Symptoms of Schizophrenia

The drug being tested in this study is called TAK-831. TAK-831 is being tested to treat
negative symptoms in participants who have schizophrenia.

The study will enroll approximately 234 participants. Participants will then be randomly
assigned (by chance, like flipping a coin) to one of the four treatment groups in the
double-blind period—which will remain undisclosed to the participant and study doctor during
the study (unless there is an urgent medical need):

- TAK-831 50 mg once daily

- TAK-831 125 mg once daily

- TAK-831 500 mg once daily

- Placebo once daily

This multi-center trial will be conducted in the North America and Europe. The overall time
to participate in this study is approximately 20 weeks. Participants will make 11 visits to
the clinic, and will be followed up for safety assessment 10 to 14 days after the last dose
of study drug (Day 98).

Inclusion Criteria:

1. Has a current diagnosis of schizophrenia as defined by the Mini International
Neuropsychiatric Interview (MINI) 7.0.2 for Psychotic Disorders for the Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The participant's
initial diagnosis must be greater than or equal to (>=) 1 year from screening.

2. Is receiving primary background antipsychotic therapy at a total daily dose between 2
and 6 mg of risperidone equivalents. Concomitant treatment with a sub-therapeutic dose
of a second antipsychotic may be permitted with sponsor or designee approval if used
as a hypnotic (for example quetiapine 100 mg or its equivalent once daily at bedtime
[QHS]), but not if it is used for refractory positive psychosis symptoms).

3. Is treated with a stable regimen of psychotropic medications with no clinically
meaningful change (no increase in dose, less than or equal to [<=] 25 percent [%]
decrease in dose for tolerability) the 2 months prior to the screening visit and no
dose adjustment is anticipated throughout study participation.

4. Has a BNSS total score (12-item, excluding number 4) >=28; stable Single-blind Placebo
Run-in and baseline BNSS total scores <= 20% change from the screening score).

5. Has no more than moderate-severe (<=5) rating on PANSS positive symptom items P1, P3,
P4, P5, P6, or unusual thought content (G9), with a maximum of 2 of these items rated
'5'; no more than moderate (<=4) rating on conceptual disorganization (P2).

6. There is evidence that the participant has stable symptomatology >=3 months prior to
the screening visit (example, no hospitalizations for schizophrenia, no emergency room
admission due to symptoms of schizophrenia, no increase in level of psychiatric care
due to worsening of symptoms of schizophrenia).

7. Have an adult informant (example, family member, social worker, caseworker,
residential facility staff, or nurse who spends >=4 hours/week with the participant)
considered reliable by the investigator who will be able to provide input for
completing study rating scales, including the PANSS and SCoRS. The informant must be
able and willing to provide written informed consent and to participate in at least 1
in-person interview, then be able to provide input by attending each clinical
assessment visit or via participating in a telephone interview for other study visits
that include the PANSS or SCoRS endpoints.

Exclusion Criteria:

1. 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
combined with the general psychiatric evaluation.

2. 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.

3. 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.

4. Is participating in a formal structured nonpharmacological psychosocial therapeutic
treatment program (cognitive remediation, cognitive-behavioral therapy, intensive
symptom/vocational rehabilitation) for a duration of less than (<) 3 months prior to
randomization. In addition, initiation of such nonpharmacological treatment programs
is not permitted during study participation through the Day 84 visit.

5. The participant exhibits more than a minimal level of antipsychotic-induced
parkinsonism symptoms, as documented by a score on the modified Simpson Angus Scale
(SAS) (excluding item number 10, Akathisia) greater than (>) 6.

6. Has evidence of depression as measured by a Calgary Depression Scale Score (CDSS) > 9.

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

8. Has a history of brain trauma associated with loss of consciousness for >15 minutes.

9. Diagnosis of schizophrenia occurred prior to 12 years of age.

10. Has received electroconvulsive therapy within 6 months (180 days) before Screening.

11. Has a history of developmental intellectual disability or mental retardation.

12. Antipsychotic plasma levels for the participant's primary background antipsychotic are
below the minimum acceptable concentration criteria per the Antipsychotic Drug Level
Reference Document at the Screening or Placebo Run-in Visits. This criterion is not
applicable to participants on a primary background antipsychotic for which a clinical
assay is unavailable.

13. Has received clozapine for the treatment of schizophrenia within a 6-month period
before screening.

14. Does not have a stable residence or is homeless.