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

Study Overview
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Brief Summary
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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
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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 42mg/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
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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
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Lumateperone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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 and at Baseline; Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥14 at Screening and at Baseline; 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 buproprion 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
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Åsberg 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
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Keywords Provided by Centre Hospitalier Valida
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Adjunctive MDD Therapy