Study to Evaluate the Efficacy and Safety of 3 Fixed Doses of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Pediatric Participants Assessed to be at Imminent Risk for Suicide

NCT03185819 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR1083232016-004422-42ESKETINSUI2002
• Study Type: interventional
• Target: 147
• Locations: 9 countries
• Sites: 51

Brief Summary

The purpose of this study is to assess the efficacy of a single (first) dose of 3 fixed doses of intranasal esketamine {28 milligram (mg), 56 mg, and 84 mg} compared with psychoactive placebo (oral midazolam) in rapidly reducing the symptoms of major depressive disorder (MDD) including suicidal ideation in participants 12 to less than 18 years of age who are assessed to be at imminent risk for suicide.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at 24 Hours Post First Dose (Day 2)

  The CDRS-R is a validated 17- item, clinician-rated instrument developed to assess depressive symptomatology in children. Scores were based on interviews with both the child and their caregiver. Of the 17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed affect) rated on a 5-point scale from 1 (no depression) to 5 (severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression), where higher score indicated more severe depression. The CDRS-R total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher score indicated more severe depression and worse outcome.

  Baseline (predose on Day 1) and 24 hours post first dose on Day 1 (i.e., Day 2)

Study Arms (4)

Oral Midazolam + Intranasal Placebo

PLACEBO COMPARATOR

Participants will receive midazolam solution 0.125 milligram per kilogram (mg/kg) orally 2 times per week for 4 weeks and 3 intranasal doses of matched placebo to esketamine.

Drug: Intranasal Placebo; Drug: Midazolam

Oral Placebo + Esketamine 84 mg

EXPERIMENTAL

Participants will receive intranasal esketamine 84 mg as 3 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks.

Drug: Midazolam Placebo Solution; Drug: Esketamine

Oral Placebo + Esketamine 56 mg

EXPERIMENTAL

Participants will receive intranasal esketamine 56 mg as 2 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks.

Drug: Midazolam Placebo Solution; Drug: Esketamine

Oral Placebo + Esketamine 28 mg

EXPERIMENTAL

Participants will receive intranasal esketamine 28 mg as 1 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks.

Drug: Midazolam Placebo Solution; Drug: Esketamine

Interventions

Intranasal Placebo DRUG

Participants will receive placebo as intranasal dose to match intranasal esketamine.

Oral Midazolam + Intranasal Placebo

Midazolam Placebo Solution DRUG

Participants will receive placebo as oral dose to match midazolam drug.

Oral Placebo + Esketamine 28 mg; Oral Placebo + Esketamine 56 mg; Oral Placebo + Esketamine 84 mg

Midazolam DRUG

Participants will receive midazolam solution 0.125 mg/kg as oral dose to match placebo.

Oral Midazolam + Intranasal Placebo

Esketamine DRUG

Participants will receive esketamine at a dose of 28 mg as intranasal solution.

Oral Placebo + Esketamine 28 mg

Eligibility Criteria

• Age: 9 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants must meet diagnostic and statistical manual of mental disorders (5th edition) {DSM-5} diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the mini international neuropsychiatric interview for children and adolescents (MINI KID)
• Participant must have a children's depression rating scale-revised (CDRS-R) total score of equal or more than (\>=) 58 predose on Day 1
• As part of standard of care treatment, participant must agree to be hospitalized voluntarily for a recommended period of 5 days after randomization (may be shorter or longer if clinically warranted in the investigator's opinion)
• As part of the newly initiated or optimized standard of care treatment, participant must agree to take one of the prescribed non-investigational antidepressant medications (fluoxetine, escitalopram, sertraline; and 9-11 years old participants at US-sites only: fluoxetin \[preferred\], sertraline) at least during the double-blind treatment phase (Day 25)
• As part of standard of care treatment, participant must agree to participate in a specific psychological intervention (individual cognitive behavioral therapy \[CBT\], interpersonal therapy, family therapy or psychodynamic psychotherapy) at least through the initial 8-week post-treatment follow-up period (Day 81)

You may not qualify if:

• Participants has a current DSM-5 diagnosis of bipolar (or related disorders), intellectual disability, autism spectrum disorder, conduct disorder, anorexia nervosa, oppositional defiant disorder, or obsessive compulsive disorder
• Participants currently meets DSM-5 criteria for borderline personality disorder. Participants not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded
• Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychosis
• Participant has a history of seizure disorder

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (51)

Institute of Living/ Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Atlanta Behavioral Research, LLC

Atlanta, Georgia, 30338, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Neuroscience Research Institute

Winfield, Illinois, 60190, United States

Location

Beacon Medical Group Clinical Research

South Bend, Indiana, 46617, United States

Location

University of Iowa, Carver College of Medicine

Iowa City, Iowa, 52242, United States

Location

Lake Charles Clinical Trials

Lake Charles, Louisiana, 70629, United States

Location

Sheppard Pratt Health System

Baltimore, Maryland, 21204, United States

Location

CBH Health

Gaithersburg, Maryland, 20877, United States

Location

State University of New York at Buffalo

Buffalo, New York, 14215, United States

Location

University North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

University of Cincinnati Hospital

Cincinnati, Ohio, 45219, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9063, United States

Location

Hopital Erasme

Brussels, 1070, Belgium

Location

Trial Tech Tecnologia em Pesquisas com Medicamentos

Curitiba, 80240-280, Brazil

Location

Hospital Universitario Professor Edgar Santos

Salvador, 40110-060, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, 09715-090, Brazil

Location

Hospital São Sebastião

Turvo, 88930-000, Brazil

Location

Mental Health Center - Rousse

Rousse, 7003, Bulgaria

Location

Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD

Varna, Bulgaria

Location

Hospices Civils de Lyon HCL

Bron, 69677, France

Location

CHRU Lille - Hôpital Fontan 1

Lille, 59000, France

Location

CHU Nantes

Nantes, 44093, France

Location

Hôpital Universitaire Pitié-Salpêtrière

Paris, 75013, France

Location

Hopital Sainte Anne

Paris, 75014, France

Location

Hôpital Robert Debré

Paris, 75019, France

Location

Vadaskert Gyermek es Ifjusagpszichiatriai Korhaz es Szakambulancia

Budapest, Hungary

Location

Szegedi Tudomanyegyetem

Szeged, Hungary

Location

Azienda Ospedaliera G. Brotzu

Cagliari, 09134, Italy

Location

OSP RIUNITI-DIP Donna- Bambino

Foggia, 71122, Italy

Location

Ospedale di Merano

Merano, 39012, Italy

Location

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, 98125, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80138, Italy

Location

IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione

Pavia, 27100, Italy

Location

Irccs Burlo-Garofalo

Trieste, 34137, Italy

Location

Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ

Krakow, 31-501, Poland

Location

Dzieciecy Szpital Kliniczny im Jozefa Polikarpa Brudzinskiego

Warsaw, 02 091, Poland

Location

Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy

Warsaw, 02-957, Poland

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. Sant Joan de Deu

Esplugues de Llobregat, 08950, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Hosp. Infantil Univ. Nino Jesus

Madrid, 28009, Spain

Location

Hosp. Univ. Pta. de Hierro Majadahonda

Majadahonda, 28222, Spain

Location

Hosp. Univ. Central de Asturias

Oviedo, 33011, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Corporacio Sanitari Parc Tauli

Sabadell, 08208, Spain

Location

Related Publications (1)

• Kosik-Gonzalez C, Fu DJ, Chen LN, Lane R, Bloch MH, DelBello M, Moreno C, Drevets WC, Canuso CM. Effect of Esketamine on Depressive Symptoms in Adolescents With Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study. J Am Acad Child Adolesc Psychiatry. 2026 Jan;65(1):42-55. doi: 10.1016/j.jaac.2025.02.015. Epub 2025 Mar 7.

  PMID: 40058488 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Midazolam; Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Janssen-Cilag International NV

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
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 14, 2017
• Study Start: October 5, 2017
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: April 29, 2025
• Results First Posted: April 17, 2024

Record last verified: 2025-04

Locations

BE (1); BR (4); FR (6); US (18); BU (2); HU (2); IT (7); PL (3); ES (8)