Clinical Trial of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Inclusion Criteria:

Male or female patients between the ages of 18 and 65 years, inclusive;

Meets DSM-5 criteria for MDD as confirmed by using the MINI and meets all of the following criteria:

1. The start of the current major depressive episode (MDE) is at least 8 weeks but not more than 18 months prior to Screening;
2. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 at Screening and at Baseline;
3. Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening and at Baseline;
4. Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥14 at Screening and at Baseline;
5. and the current MDE is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Currently having an inadequate response to ADT (less than 50% improvement) as confirmed by the Investigator and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration:

1. citalopram/escitalopram
2. fluoxetine
3. paroxetine
4. sertraline
5. duloxetine
6. levomilnacipran/milnacipran (if locally approved for MDD)
7. venlafaxine/desvenlafaxine
8. buproprion
9. vilazodone
10. vortioxetine

Exclusion Criteria:

Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including:

1. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder;
2. Bipolar Disorder;

Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including:

1. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses.
2. Eating disorder;
3. Substance use disorders (excluding nicotine);
4. Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status;
5. Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment;
6. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline;
7. The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline;

In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or:

1. At Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit;
2. At Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening;
3. At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or
4. The patient is considered to be in imminent danger to him/herself or others.
5. The patient has a first MDE at age 60 years or older.