A Trial of the Safety and Efficacy of SEP-363856 in the Treatment of Adults With Major Depressive Disorder

Inclusion Criteria:

• Male and Female subjects between 18-65 years of age, with a primary diagnosis ofmajor depressive disorder and in a current major depressive episode

• Current major depressive episode must be at least 8 weeks and no longer than 2 yearsin duration

• History of an inadequate response to at least 1 and no more than 3 antidepressanttreatments in the current major depressive episode

Exclusion Criteria:

• Subjects who report an inadequate response to more than 3 antidepressant treatmentsin the current episode

• Subjects with a lifetime history of schizophrenia spectrum or other psychoticdisorder, bipolar or related disorder, major or mild neurocognitive disorder,neurodevelopmental disorder of greater than mild severity or of a severity thatimpacts the participant's ability to consent/ follow study directions/ or otherwisesafely participate in the study, borderline or antisocial personality disorder.

• Subjects with a current diagnosis of post-traumatic stress disorder, obsessivecompulsive disorder, panic disorder, or eating disorder (including anorexia nervosaor bulimia).

• Sexually active subjects, who could become pregnant, not agreeing to practice 2sponsor approved methods of birth control or remain abstinent during the trial andfor 30 days (females) or 90 days (males) after last dose of study drug.