Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing ADT.

Detailed Description
-----------------
The study will be conducted in three periods: Screening Period (up to 2 weeks) during which patient eligibility will be assessed; Double-blind Treatment Period (6 weeks) in which all patients will be randomized to receive placebo or lumateperone 42 mg/day in 1:1 ratio. Safety Follow-up Period (1 week) in which all patients will return to the clinic for a safety follow-up visit approximately one week after the last dose of study treatment.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: Lumateperone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients between the ages of 18 and 65 years, inclusive; Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed by the Investigator or Sponsor-approved rater using the MINI and meets all of the following criteria: The start of the current major depressive episode (MDE) is at least 8 weeks but not more than 18 months prior to Screening; Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 at Screening and at Baseline; Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening (Visit 1) and at Baseline; Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥ 14 at Screening and at Baseline; Has sufficient history and medical record confirmation verifying the ADT 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: citalopram/escitalopram fluoxetine paroxetine sertraline duloxetine levomilnacipran/milnacipran (if locally approved for MDD) venlafaxine/desvenlafaxine bupropion vilazodone vortioxetine Exclusion Criteria: Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including: Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder; Bipolar Disorder; Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including: Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Eating disorder; Substance use disorders (excluding nicotine); Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status; Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment; The patient experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline; 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: 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; At Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening; At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or The patient is considered to be in imminent danger to him/herself or others. The patient has a first MDE at age 60 years or older.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lumateperone 42 mg<br> | Drug: Lumateperone<br>* Lumateperone 42 mg capsules administered orally, once daily.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching capsules administered orally, once daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale | The MADRS is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms. | Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression Scale-Severity | The CGI-S is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Day 43 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adjunctive MDD Therapy