A clinical study to determine whether an investigational medication (SEP363856) changes how long it takes for food to move through the stomach into the small intestine in patients with schizophrenia. This study is accepting both male and female subjects. It will be conducted in approximately 6 study sites in the United States. The duration of participation will be approximtely 10 weeks.

This is a randomized, open-label, single dose two-period crossover study with two treatment sequences. For each treatment sequence, subjects will receive a single-dose of SEP-363856 and prior antipsychotic (PA) standard of care (PA) in random order. Up to 3 separate cohorts of subjects will be randomized to determine the final dose of SEP-363856.

Inclusion Criteria: (this list is not all inclusive)

• Male or female subjects between 18 and 65 years of age, inclusive at time of consent.
• Subject meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a primary diagnosis of schizophrenia as established by clinical interview, using the DSM-5 as a reference and confirmed using the Structured Clinical Interview for DSM-5, Clinical Trials Version [SCID-CT]).
• Subject must have a CGI-S score ≤ 4 (normal to moderately ill) at Screening
• Subject must have a PANSS total score ≤ 80 at Screening and a score of ≤ 4 on the following PANSS items at Screening: P7 (hostility) and G8 (uncooperativeness)
• Subjects' antipsychotic medication at screening must have had no dose change (minor dose adjustments for tolerability purposes are permitted) for at least eight weeks prior to the Screening visit.

Exclusion Criteria: (this list is not all inclusive)

• Subject has a DSM-5 diagnosis or presence of symptoms consistent with a DSM-5 diagnosis other than schizophrenia or intellectual disability (IQ < 70).

  • Subject has attempted suicide within 12 months prior to Screening.
  • Subject answers "yes" to "Suicidal Ideation" Items 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS at Screening (ie. in the past 1 month) or at any subsequent C-SSRS assessment prior to dosing (ie, since last visit).
  • Subject is at risk of harming him/herself or others according to the Investigator's judgment.

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.