The purpose of this study is to determine whether improvement in P50 (a pharmacodynamic marker) in auditory sensory gating is demonstrated after administration of TAK-058 and ondansetron compared to placebo in participants with schizophrenia.

The drug being tested in this study is called TAK-058. TAK-058 is being tested to evaluate its effects on P50 auditory gating in people who have stable schizophrenia. This study will look at the effect of TAK-058 on P50 auditory gaiting of people with schizophrenia.

This study will be performed in a sequential manner progressing from an optimization (screening) phase in healthy volunteers, to screening of subjects with schizophrenia in part 1, to a 3 period crossover treatment phase in part 2. In the screening phase, 15 healthy volunteers will be enrolled to optimize the settings for the measurement of neurophysiological markers prior to any dosing in participants with schizophrenia. If optimization is not reached, the study will be terminated. In part 1 participants with schizophrenia will receive 2 P50 electroencephalography (EEG) sessions. A measurable deficit in auditory P50 gating S2/S1 ratio greater than (>) 0.5 will be established during this phase. The intraclass correlation coefficient (ICC) will be calculated for the P50 auditory gating S2/S1 ratios collected during the 2 sessions. If these P50 auditory gating S2/S1 ratio measurements are found to have at least a fair level of agreement within individuals (that is, ICC > 0.5), part 2 of the study will begin. 12 participants demonstrating P50 impairment in part 1, will be randomly assigned (by chance, like flipping a coin) to one of the six treatment crossover sequences -which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Placebo + TAK-058 + Ondansetron
• TAK-058 + Placebo + Ondansetron
• Ondansetron + Placebo + TAK-058
• Placebo + Ondansetron + TAK-058
• TAK-058 + Ondansetron + Placebo
• Ondansetron + TAK-058 + Placebo

All participants will be asked to take one dose of capsule, followed 1 hour later by one dose of solution on Day 1 of each intervention period.

This single-center trial will be conducted in the United States. The overall time to participate in this study is approximately 118 days. Participants will make be confined to the clinic for 3 days (Day -1 through Day 2 of each period), a final visit for schizophrenic participants in Part 2 after receiving TAK-058, on Day 2 of Period 3 (no final visit for optimization phase healthy participants), and a telephonic follow up assessment 21 days after last dose of study drug.

Inclusion Criteria:

1. 18 to 60 years of healthy and schizophrenic participants, inclusive, at the time of informed consent.
2. Has acceptable clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis).
3. Meets schizophrenia criteria as defined by the Diagnostic & Statistical Manual of Mental Disorders, 5th Edition (DSM-V).
4. Are on a stable dose of single second-generation antipsychotics (SGA) for at least 2 months prior to Screening as documented by medical history and assessed by site staff.
5. Demonstrates Positive and Negative Syndrome Scale (PANSS) total score of less than equal to (<=) 85.
6. Has a P50 ratio of > 0.5 at both screening assessments.

Exclusion Criteria:

1. Has a history in the last year or currently receiving treatment with clozapine or olanzapine.
2. Has taken any excluded medications, supplements or food products.
3. Has a history of gastrointestinal disease that would influence the absorption of study drug or have a significant medical history of any disease that would contraindicate the administration of TAK-058, ondansetron, or a similar compound.
4. Has substance abuse or dependence within previous 12 months, unstable mood or anxiety disorder.
5. Has a current diagnosis of a significant psychiatric illness other than schizophrenia per DSM-V and is in an acute phase/episode.
6. Has clinically meaningful hearing loss per investigator's judgment.

Schizophrenia Set included all participants who were enrolled and completed the Screening Phase (Part-1) of the study.

Day 1 of Period 1 of Part 2, up to 21 days after last dose of study drug in Part 2

No AE assessments were done because AEs were planned to be collected in Treatment Phase (Part-2) of the study which was not initiated because it was not possible to calculate an ICC due to the magnitude of the intrasubject variability in relation to the intersubject variability.