Study of Rapastinel as Monotherapy in Major Depressive Disorder (MDD)

Study Overview
=================
Brief Summary
-----------------
The study will evaluate the efficacy, safety, and tolerability of 450 milligrams (mg) of Rapastinel, compared to 10 mg of Vortixetine and placebo in participants with major depressive disorder (MDD).

Official Title
-----------------
A Randomized, Double-blind, Placebo- and Active- Controlled, Multicenter Study of Rapastinel as Monotherapy in Major Depressive Disorder

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

Intervention / Treatment
-----------------
* Drug: Rapastinel
* Drug: Vortioxetine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD Current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1 Have inadequate response to 1-3 antidepressant therapies given at adequate dose and duration in the current episode If female of childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test Exclusion Criteria: DSM-5-based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1 Lifetime history of meeting DSM-5 criteria for: Schizophrenia spectrum or other psychotic disorder Bipolar or related disorder Major neurocognitive disorder Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study Dissociative disorder Posttraumatic stress disorder MDD with psychotic features Significant suicide risk, as judged by the Investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapastinel<br>Rapastinel (450 mg prefilled syringe, weekly intravenous IV administration). | Drug: Rapastinel<br>* Rapastinel (prefilled syringe, weekly intravenous IV administration).<br>|
| Active Comparator: Vortioxetine<br>Vortixetine (10 mg with available dose increase to vortioxetine 20 mg oral daily after 3 weeks of administration). | Drug: Vortioxetine<br>* Vortixetine (10 mg with available dose increase to vortioxetine 20 mg oral daily after 3 weeks of administration).<br>|
| Placebo Comparator: Placebo<br>Placebo (prefilled syringe, weekly IV administration or oral daily). | Drug: Placebo<br>* Placebo (prefilled syringe, weekly IV administration or oral daily).<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at the End of the Double Blind Treatment Period (DBTP) (end of Week 6) | The MADRS, a clinician-rated scale, will be used to assess depressive symptomatology. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item will be scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity. | Baseline to end of Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in MADRS Total Score at Day 1 Post-first Dose of Treatment | The MADRS, a clinician-rated scale, will be used to assess depressive symptomatology. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item will be scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity. | Baseline to Day 1 post-first dose |