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

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

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major; Suicidal
• Intervention / Treatment: Drug: Placebo; Drug: SLS-002; Other: Standard of care; Device: Intranasal device

Detailed Description

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/

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Seelos Investigational Site
    • Panorama City, California, United States, 91402
      • Seelos Investigational Site
    • San Diego, California, United States, 92103
      • Seelos Investigational Site
  • Florida
    • Hollywood, Florida, United States, 33021
      • Seelos Investigational Site
    • Miami, Florida, United States, 33144
      • Seelos Investigational Site
    • Miami Lakes, Florida, United States, 33016
      • Seelos Investigational Site
    • Miramar, Florida, United States, 33025
      • Seelos Investigational Site
    • Oakland Park, Florida, United States, 33324
      • Seelos Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Seelos Investigational Site
    • Decatur, Georgia, United States, 30030
      • Seelos Investigational Site
  • Illinois
    • Springfield, Illinois, United States, 62781
      • Seelos Investigational Site
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Seelos Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Seelos Investigational Site
  • New York
    • Buffalo, New York, United States, 14215
      • Seelos Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Seelos Investigational Site
    • North Canton, Ohio, United States, 44720
      • Seelos Investigational Site
  • Texas
    • DeSoto, Texas, United States, 75115
      • Seelos Investigational Site
    • Houston, Texas, United States, 77054
      • Seelos Investigational Site
    • Richardson, Texas, United States, 75080
      • Seelos Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Seelos Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Seelos Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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 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 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 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 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 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 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 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)
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)

Collaborators and Investigators

• Sponsor: Seelos Therapeutics, Inc.

Publications and helpful links

Helpful Links

• Study information portal

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2020
• Primary Completion (Actual): June 17, 2023
• Study Completion (Actual): July 14, 2023

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Depression; Ketamine; Suicide; Mental disorders; Suicidal Ideation; Self-injurious behavior; Behavioral symptoms; Depressive disorder; Mood disorders; Psychotropic drugs; SLS-002; Antidepressive agents
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Self-Injurious Behavior; Depression; Depressive Disorder; Suicide; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: SLS-002-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes