A Study of SLS-002 (Intranasal Racemic Ketamine) in Adults With Major Depressive Disorder at Imminent Risk of Suicide

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy, safety, and tolerability of SLS-002 (intranasal racemic ketamine) in addition to standard of care on symptoms of Major Depressive Disorder (MDD) and suicidality, in participants who are assessed to be at imminent risk for suicide, as measured by the change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24 hours post first dose.

Detailed Description
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This is a 2-part study: Part 1 is open-label, while Part 2 is a randomized, double-blind, placebo-controlled, multicenter study. The study will enroll participants with MDD for whom a physician has assessed to be at risk for suicide. The study will consist of a screening evaluation, a treatment period, and a safety follow-up period. Participants' safety will be evaluated throughout the study. If you or a loved one are having thoughts of suicide, please seek immediate medical help. Go to the emergency room or call the National Suicide Prevention Lifeline at 1-800-273-8255. Potential participants may visit http://frontiersstudy.com/

Official Title
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A 2-part Phase 2 Study to Assess the Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) Administered to Adults With Major Depressive Disorder at Imminent Risk of Suicide

Conditions
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Depressive Disorder, Major, Suicidal

Intervention / Treatment
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* Drug: SLS-002
* Drug: Placebo
* Other: Standard of care
* Device: Intranasal device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant with diagnosis of current MDD (unipolar without psychotic features) per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with symptoms present for at least 4 weeks, based on psychiatric intake and confirmed by the Mini International Psychiatric Interview Version 7.02 for Suicidality Disorders (MINI). Participant has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of ≥28 predose on Day 1, and has a score of 5 or 6 on item 10. Participant has a Clinical Global Impression of Severity for Suicidal Ideation and Behavior (CGIS-SI/B) score of ≥4 predose on Day 1. Participant requires psychiatric hospitalization due to significant risk of suicide, has ≥15 on the S-STS CMCM total score, and a score of 6-9 (inclusive) on the S-STS CMCM Clinician judgment of subject's risk of a suicide attempt or death by suicide at this time. Participant has a history of previous suicide attempt(s), as confirmed on the Columbia Suicide Severity Rating Scale (C-SSRS) with a history of at least one actual attempt, or if the attempt was interrupted or aborted, is judged to have been serious in intent. Participant is willing and able to take prescribed non-investigational antidepressant therapy(ies) at investigator's discretion for at least the duration of the study. Exclusion Criteria: Participant has seizures, intellectual disability, a neurocognitive disorder or a lifetime diagnosis of bipolar disorder, any mood disorder with psychotic features, schizophrenia or other psychotic disorder, obsessive compulsive disorder, or antisocial personality disorder. In the investigator's opinion, participant has chronic, refractory treatment-resistant depression from >4 adequate therapeutic trials of antidepressants (with or without adjuvants and/or ECT) as confirmed by Antidepressant Treatment Response Questionnaire (ATRQ). Participant has a body mass index (BMI) >40 or <18 at screening, uncontrolled hypertension, or any clinically significant medical condition that might confound the results. Participant meets the DSM-5 criteria for moderate or severe substance use disorder or a positive urine test for drugs of abuse. Participant does not meet or is not willing to comply with the requirements listed in prohibited and restricted medications and therapies in the protocol, as well as required washout periods prior to participation.

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
Interventional Model Description: Part 1 is a single group. Part 2 is a parallel group 1:1 randomization of SLS-002 to placebo, plus standard of care.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLS-002 + Standard of care<br>Participants will receive SLS-002 (intranasal racemic ketamine) 90 milligram (mg) two times per week for 2 weeks with standard of care treatment | Drug: SLS-002<br>* Intranasal racemic ketamine hydrochloride 90 milligrams (mg)<br>* Other names: Ketamine hydrochloride;Other: Standard of care<br>* Standard of care treatment will be determined by the treating physician(s) based on clinical judgement and practice guidelines<br>Device: Intranasal device<br>* Device to deliver intranasal solution<br>|
| Placebo Comparator: Placebo + Standard of care<br>Participants will receive intranasal placebo two times per week for 2 weeks with standard of care treatment | Drug: Placebo<br>* Intranasal placebo<br>Other: Standard of care<br>* Standard of care treatment will be determined by the treating physician(s) based on clinical judgement and practice guidelines<br>Device: Intranasal device<br>* Device to deliver intranasal solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at 24 Hours Post First Dose | MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. | Baseline (Day 1, predose) and 24 hours post first dose (Day 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Day 16 | MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. | Baseline (Day 1, predose) and 2 weeks post first dose (Day 16) | 
| Change From Baseline in Clinical Global Impression of Severity for Suicidal Ideation and Behavior (CGIS-SI/B) Scale at 24 Hours Post First Dose | Clinical global impression of severity for suicidal ideation and behavior (CGIS-SI/B) scale is revised version of the clinical global impression severity scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participant's illness. The CGIS-SI/B summarizes the clinician's overall impression of severity of suicidal ideation and behavior on a 5-point scale from 1 (not at all suicidal) to 5 (among the most extremely suicidal), based on the totality of information available to the clinician. | Baseline (Day 1, predose) and 24 hours post first dose (Day 2) | 
| Change From Baseline in Patient Global Impression of Severity for Suicidal Ideation and Behavior (PGIS-SI/B) Scale at 24 Hours Post First Dose | Patient global impression of severity for suicidal ideation and behavior (PGIS-SI/B) scale is revised version of the patient global impression severity scale (PGI-S), a global rating scale that gives the patient's perspective on their overall severity of suicidal impulses, thoughts, and behaviors. The PGIS-SI/B summarizes the patient's overall impression of severity of suicidal ideation and behavior on a 5-point scale from 1 (not present) to 5 (extremely severe). | Baseline (Day 1, predose) and 24 hours post first dose (Day 2) | 
| Change From Baseline in Clinical Global Impression of Severity for Suicidal Ideation and Behavior (CGIS-SI/B) Scale at Day 16 | Clinical global impression of severity for suicidal ideation and behavior (CGIS-SI/B) scale is revised version of the clinical global impression severity scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participant's illness. The CGIS-SI/B summarizes the clinician's overall impression of severity of suicidal ideation and behavior on a 5-point scale from 1 (not at all suicidal) to 5 (among the most extremely suicidal), based on the totality of information available to the clinician. | Baseline (Day 1, predose) and 2 weeks post first dose (Day 16) | 
| Change from Baseline in Sheehan-Suicidality Tracking Scale Clinically Meaningful Change Measure (S-STS CMCM) Total Score at 24 hours post first dose (Day 2) | The Sheehan-Suicidality Tracking Scale Clinically Meaningful Change Measure (S-STS CMCM) is a clinician-rated outcome measure which assesses suicidal ideation and behavior on a standard 22-item scale, as well as multiple patient and clinician-rated items. The first 16 items are rated on a Likert-type scale ranging from 0 = not at all to 4 = extremely, where select scoring (i.e., 4 specific items are scored based on the highest score on 2 of those items) yields a total score ranging from 0 to 52. | Baseline (Day 1, predose) and 24 hours post first dose (Day 2) | 
| Change From Baseline in Patient Global Impression of Severity for Suicidal Ideation and Behavior (PGIS-SI/B) Scale at Day 16 | Patient global impression of severity for suicidal ideation and behavior (PGIS-SI/B) scale is revised version of the patient global impression severity scale (PGI-S), a global rating scale that gives the patient's perspective on their overall severity of suicidal impulses, thoughts, and behaviors. The PGIS-SI/B summarizes the patient's overall impression of severity of suicidal ideation and behavior on a 5-point scale from 1 (not present) to 5 (extremely severe). | Baseline (Day 1, predose) and 2 weeks post first dose (Day 16) | 
| Change from Baseline in Sheehan-Suicidality Tracking Scale Clinically Meaningful Change Measure (S-STS CMCM) Total Score at Day 16 | The Sheehan-Suicidality Tracking Scale Clinically Meaningful Change Measure (S-STS CMCM) is a clinician-rated outcome measure which assesses suicidal ideation and behavior on a standard 22-item scale, as well as multiple patient and clinician-rated items. The first 16 items are rated on a Likert-type scale ranging from 0 = not at all to 4 = extremely. | Baseline (Day 1, predose) and 2 weeks post first dose (Day 16) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Depressive disorder, SLS-002, Mental disorders, Suicide, Suicidal Ideation, Mood disorders, Behavioral symptoms, Self-injurious behavior, Ketamine, Antidepressive agents, Psychotropic drugs