A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for Suicide

NCT02133001 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CR103162ESKETINSUI2001
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study is to evaluate the efficacy of intranasal esketamine 84 milligram (mg) compared with intranasal placebo along with standard care treatment, in reducing the symptoms of major depressive disorder (MDD) (an affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities, the mood disturbance is prominent and relatively persistent), including the risk for suicide as assessed by the Investigator, in participants who will be assessed to be at imminent risk for suicide.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; Esketamine; Intranasal esketamine; Placebo

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Day 1: 4-Hour Post-dose in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Double-blind Phase)

  The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The last observation carried forward (LOCF) approach was used for missing visit data in the ITT LOCF efficacy analyses.

  Baseline (Day 1-Predose) to Day 1: 4-hours post-dose

Secondary Outcomes (19)

• Percentage of Participants With Sustained Response Based on MADRS Total Score (Double-blind Phase)

  Day 1 to Day 25

• Change From Baseline to Day 2 in MADRS Total Score (Double-blind Phase)

  Baseline (Day 1-predose) to Day 2

• Change From Baseline to Double-blind Phase-End Point (Day 25) in MADRS Total Score (Double-blind Phase)

  Baseline (Day 1-predose) to Double-blind Phase-End Point (Day 25)

• Percentage of Participants With Response Based on MADRS Total Score During the Double-Blind Phase

  Day 1 (4 hours postdose), Day 2 (double blind phase), Double blind phase -Endpoint (Day 25)

• Percentage of Participants With Response Based on MADRS Total Score at Follow up Phase Endpoint

  Follow up phase-endpoint (Day 81)

Study Arms (2)

Esketamine

EXPERIMENTAL

Esketamine hydrochloride solution (containing 14 milligram (mg) of esketamine base per 100 microliter \[mcl\] of intranasal spray) will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks. Dose may be reduced to 56 mg per day based on Investigator's discretion.

Drug: Esketamine

Placebo

PLACEBO COMPARATOR

Matching Placebo solution will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks.

Drug: Placebo

Interventions

Esketamine DRUG

Esketamine 84 mg will be self-administered by participants as intranasal spray as two times a week, for 4 weeks (that is, Day 1,4,8,11,15,18,22,25). Dose may be reduced to 56 mg per day based on Investigator's discretion.

Also known as: Esketamine hydrochloride

Esketamine

Placebo DRUG

Matching placebo will be self-administered by participants as intranasal spray as two times a week, for 4 weeks (that is, Day 1,4,8,11,15,18,22,25).

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for major depressive disorder
• Participants must have current suicidal ideation with intent
• In the Investigator's opinion, participant must be in need of acute psychiatric hospitalization due to imminent risk of suicide
• Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than or equal to (\>=) 22 predose on Day 1
• As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 5 days after randomization (that is, through Day 5), and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)

You may not qualify if:

• Participant has a current clinical diagnosis of bipolar or related disorders, intellectual disability, or cluster b personality disorder (example, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder)
• Participant meets DSM-IV criteria for borderline personality disorder, based on clinical interview
• Participant has a current or prior diagnosis of a psychotic disorder, major depressive disorder (MDD) with psychosis, or obsessive compulsive disorder
• Participant with a history or current signs and symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances
• Participant has uncontrolled hypertension (systolic blood pressure greater than \[\>\] 160 millimeter of mercury \[mmHg\] or diastolic blood pressure \> 90 mmHg) despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment at Screening; or any past history of hypertensive crisis

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (14)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Hartford, Connecticut, United States

Location

Unknown Facility

New Haven, Connecticut, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Iowa City, Iowa, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Towson, Maryland, United States

Location

Unknown Facility

Ann Arbor, Michigan, United States

Location

Unknown Facility

Rochester, Minnesota, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Related Publications (2)

• Perez-Ruixo C, Rossenu S, Zannikos P, Nandy P, Singh J, Drevets WC, Perez-Ruixo JJ. Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. Clin Pharmacokinet. 2021 Apr;60(4):501-516. doi: 10.1007/s40262-020-00953-4. Epub 2020 Oct 31.

  PMID: 33128208 DERIVED

• Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Am J Psychiatry. 2018 Jul 1;175(7):620-630. doi: 10.1176/appi.ajp.2018.17060720. Epub 2018 Apr 16.

  PMID: 29656663 DERIVED

Related Links

• A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who are Assessed to be at Imminent Risk for Suicide

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Senior Medical Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 7, 2014
• Study Start: May 23, 2014
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: April 29, 2025
• Results First Posted: April 24, 2019

Record last verified: 2025-04

Locations

US (14)