A Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Adults With Schizophrenia

Inclusion Criteria

• Subject must give written informed consent and privacy authorization prior to participation in the study. Separate consent will be obtained from a caregiver or legal guardian if required by local law.
• Subject must be willing and able to comply with the study procedures and visit schedules, including required hospitalization for the washout period and the double-blind treatment period, and must be able to understand and follow verbal and written instructions.
• Male or female subject between 18 to 40 years of age (inclusive) at the time of consent.
• Subject meets DSM-5 criteria for schizophrenia as established by clinical interview (using the DSM-5 as a reference and confirmed using the SCID-CT). The duration of the subject's illness whether treated or untreated must be ≥ 6 months.
• Subject must have a CGI-S score ≥ 4 (moderate or greater) at screening and Baseline (Day 1).
• Subject must have a PANSS total score ≥ 80 and a PANSS item score ≥ 4 (moderate) on 2 or more of the following PANSS items: delusions, conceptual disorganization, hallucinations, and unusual thought content at screening and Baseline (Day 1).
• Subject has an acute exacerbation of psychotic symptoms (no longer than 2 months).
• Subject has marked deterioration of functioning in one or more areas, such as occupational, social, or personal care or hygiene.
• Subject requires hospitalization for an acute psychotic exacerbation at the time of screening or has been hospitalized for the purpose of treating an acute psychotic exacerbation for no more than 2 consecutive weeks immediately before screening.

Subjects who have been hospitalized for more than 2 weeks for reasons unrelated to an acute psychotic exacerbation may be included if such a hospitalization was for a condition other than an acute psychotic relapse. For example, subjects in a long-term hospital setting who have an acute exacerbation and are transferred to an acute unit are eligible for the study.

• Subject has had no more than 2 prior hospitalizations for the treatment of an acute exacerbation of schizophrenia (not including the current hospitalization) This history must be confirmed based on report by a reliable informant (eg., caregiver or family member) or medical records available at the time of screening.
• Subject's BMI must be at least 18 kg/m2 but no more than 35 kg/m2.
• Female subject must have a negative serum pregnancy test at screening.11. Female subject of reproductive potential agrees to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after the last dose of study drug has been taken. In the Investigator's judgment, the subject will adhere to this requirement.
• Adequate contraception is defined as continuous use of either two barrier methods (eg, condom and spermicide or diaphragm with spermicide) or a hormonal contraceptive.

Acceptable hormonal contraceptives include the following: a) contraceptive implant (such as Norplant®) implanted at least 90 days prior to screening; b) injectable contraception (such as medroxyprogesterone acetate injection) given at least 14 days prior to screening; or c) oral contraception taken as directed for at least 30 days prior to screening.

• Subjects who are of non-reproductive potential, ie, subject who is surgically sterile, has undergone tubal ligation, or is postmenopausal (defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle stimulating hormone (FSH) concentrations within postmenopausal range as determined by laboratory analysis) are not required to remain abstinent or use adequate contraception.
• Female subject of reproductive potential agrees to remain abstinent or use highly effective and reliable contraception throughout the study and for at least 30 days after the last dose of study drug has been taken (See Section 21 Appendix II Highly Effective Protocol SEP361-201,