Anxiety & Depression Association of America

Open-Label of SPN-820 in Adults With Major Depressive Disorder

This study will evaluate the efficacy and safety of SPN-820 in Adults With Major Depressive Disorder (MDD)

Male or female subject, aged 18 to 65 years (inclusive) at screening. - Diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) for either recurrent or single episode MDD without psychotic features that is confirmed by the Mini International Neuropsychiatric Interview (MINI) at screening. - MADRS total score of ≥22 for the current major depressive episode (MDE) at screening and baseline (day 1) before SM administration. - CGI-S score of ≥4 (moderately ill or worse) at screening and baseline (day 1) before SM administration. - Stable, therapeutic dose of one of the following protocol-defined ADTs for the current MDE for ≥4 weeks prior to screening: citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine (immediate release or extended release), desvenlafaxine, vilazodone, levomilnacipran, vortioxetine, bupropion, or dextromethorphan/bupropion. - Stable therapeutic dose of the approved ADT throughout the study.

MADRS total score improvement of ≥25% from the highest to the lowest score from screening to baseline. - Clinically significant abnormal laboratory profiles, vital sign measurements, or ECGs prior to baseline. - History of psychotic disorder, including but not limited to schizophrenia, MDD with psychotic features, or bipolar I/II disorder with and without psychotic features. - Diagnosis within the last 12 months before screening or current diagnosis of PTSD, OCD, panic disorder, acute stress disorder, or has a history of intellectual disability, autism, or cluster A or B personality disorder. - Suicidal behavior or suicidal ideation of type 4 or type 5 based on the C-SSRS in the 2 years before screening; a history of suicide attempt in the last 6 months; or more than 2 lifetime suicide attempts. - History of substance use disorder within 6 months prior to screening or is currently using or has a positive result (urine drug screen) at screening or baseline for drugs of abuse. - History of alcohol use disorder within 6 months prior to screening. - In the investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason.

Arm	Description	Assigned Intervention
Other SPN-820 6 x 400 mg capsules		Drug: NV-5138 NV-5138 is a novel , orally bioavailable, activator of mTORC1 Other names: SPN-820

Gianpiera Ceresoli-Borroni, PhD
3018382521
gceresoliborroni@supernus.com

This is an open-label, single-group study of adjunctive SPN-820 in adults with MDD