This is a double-blind, randomized, multiple dose study in male and female adult subjects with schizophrenia. Subjects will undergo structural magnetic resonance abdominal imaging (MRI) scans as well as hyperinsulinemic euglycemic clamp (HEC) also known as "glucose clamp", after the check-in and towards the end of the treatment phase. Subjects will be randomized to SEP-363856 or their prior antipsychotic (PA). Subjects randomized to SEP-363856 will undergo blinded wash out of their PA, subsequent SEP-363856 blinded titration and 15 day of well tolerated SEP-363856 exposure. Subjects randomized to their prior antipsychotic (PA), will undergo pseudo PA washout, followed by pseudo-titration and 15 day of well tolerated PA exposure. Subjects will be discharged after subject is stable. All subjects will return to the clinic 7 + 2 days post discharge for follow-up assessments.