A Clinical Trial to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic People With Schizophrenia, Followed by an Open-label Extension Phase

Inclusion Criteria:

1. Must be fully informed of and understand the objectives, procedures, and possiblebenefits and risks of the study, and give written informed consent prior to performingany study related activities. If the subject is considered a minor according to localregulations at the time of collection of the informed consent, written consent will beobtained from a legally acceptable representative (guardian) in addition to thatobtained from the subject.
2. Male or female between 18 to 65 years of age (inclusive) at the time of consent.
3. Must meet DSM 5 criteria for schizophrenia as established by clinical interview atScreening
4. Must have a CGI S score ≥ 4 (moderately ill) at Screening and Baseline.
5. Must have a PANSS total score ≥ 80 and a PANSS item score ≥ 4 (moderate) on 2 or moreof the following PANSS items: delusions (P1), conceptual disorganization (P2),hallucinations (P3), and unusual thought content (G9) at Screening and Baseline.
6. Must have an acute exacerbation of psychotic symptoms (no longer than 2 months priorto providing informed consent for this study). The acute exacerbation should include: a. Marked deterioration of functioning in one or more areas, such as occupational,social, or personal care or hygiene.
7. In the opinion of the Investigator, subjects must be generally healthy based onScreening medical history, physical examination (PE), vital signs, ECG, and clinicallaboratory values (hematology, chemistry, and urinalysis).

Exclusion Criteria:

1. Have a DSM 5 diagnosis or presence of symptoms consistent with a DSM 5 diagnosis otherthan schizophrenia. Exclusionary disorders include but are not limited to alcohol usedisorder (within past 12 months), substance (other than nicotine or caffeine) usedisorder within past 12 months, or lifetime history of significant substance abusethat, in the opinion of the Investigator, may have had a significant and potentiallypermanent impact on the brain or other body systems, major depressive disorder,bipolar I or II disorder, schizoaffective disorder, obsessive compulsive disorder, andposttraumatic stress disorder. Symptoms of mild to moderate mood dysphoria or anxietyare allowed so long as these symptoms have not been a focus of primary treatment
2. At significant risk of harming self, others, or objects based on Investigator'sjudgment.
3. Have any clinically significant unstable medical condition or any clinicallysignificant chronic disease that in the opinion of the Investigator, would limit thesubject's ability to complete and/or participate in the study.
4. Female subjects who are pregnant or lactating.
5. Have any clinically significant abnormal laboratory value(s) at Screening (hematology,chemistry, and urinalysis) as determined by the Investigator.