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

NCT ID: NCT03185819

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-05
• Study Completion Date: 2023-03-31

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.

Detailed Description

This study will enroll participants with major depressive disorder (MDD) presenting with suicidal ideation who are assessed to be at imminent risk for suicide. The study will be conducted in 4 phases: a screening evaluation performed within 48 hours prior to Day 1 intranasal dose; a 25-day double-blind treatment phase (Days 1-25); an 8-week initial post-treatment phase (Days 25-81); and a subsequent phase to complete a full 6-month post-treatment follow-up (Days 81-200). Efficacy, safety, pharmacokinetic, biomarker, and pharmacogenomic evaluations will be performed in the study at defined schedule. The duration of the participant's participation will be approximately 29 weeks. 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.

Conditions

Depressive Disorder, Major

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Oral Midazolam + Intranasal Placebo

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.

Group Type: PLACEBO_COMPARATOR

Intranasal Placebo

Intervention Type: DRUG

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

Midazolam

Intervention Type: DRUG

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

Oral Placebo + Esketamine 84 mg

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.

Group Type: EXPERIMENTAL

Midazolam Placebo Solution

Intervention Type: DRUG

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

Esketamine

Intervention Type: DRUG

Participants will receive esketamine at a dose of 84 mg as intranasal solution.

Oral Placebo + Esketamine 56 mg

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.

Group Type: EXPERIMENTAL

Midazolam Placebo Solution

Intervention Type: DRUG

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

Esketamine

Intervention Type: DRUG

Participants will receive esketamine at a dose of 56 mg as intranasal solution.

Oral Placebo + Esketamine 28 mg

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.

Group Type: EXPERIMENTAL

Midazolam Placebo Solution

Intervention Type: DRUG

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

Esketamine

Intervention Type: DRUG

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

Interventions

Intranasal Placebo

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

Intervention Type: DRUG

Midazolam Placebo Solution

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

Intervention Type: DRUG

Midazolam

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

Intervention Type: DRUG

Esketamine

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

Intervention Type: DRUG

Esketamine

Participants will receive esketamine at a dose of 56 mg as intranasal solution.

Intervention Type: DRUG

Esketamine

Participants will receive esketamine at a dose of 84 mg as intranasal solution.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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 meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder (except for nicotine or caffeine) within the 6 months before screening. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary
• Participant has a history of seizure disorder

• Minimum Eligible Age: 9 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Institute of Living/ Hartford Hospital

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Atlanta Behavioral Research, LLC

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Neuroscience Research Institute

Winfield, Illinois, United States

Beacon Medical Group Clinical Research

South Bend, Indiana, United States

University of Iowa, Carver College of Medicine

Iowa City, Iowa, United States

Lake Charles Clinical Trials

Lake Charles, Louisiana, United States

Sheppard Pratt Health System

Baltimore, Maryland, United States

CBH Health

Gaithersburg, Maryland, United States

State University of New York at Buffalo

Buffalo, New York, United States

University North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

University of Cincinnati Hospital

Cincinnati, Ohio, United States

University Hospital of Cleveland

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Hopital Erasme

Brussels, , Belgium

Trial Tech Tecnologia em Pesquisas com Medicamentos

Curitiba, , Brazil

Hospital Universitario Professor Edgar Santos

Salvador, , Brazil

CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, , Brazil

Hospital São Sebastião

Turvo, , Brazil

Mental Health Center - Rousse

Rousse, , Bulgaria

Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD

Varna, , Bulgaria

Hospices Civils de Lyon HCL

Bron, , France

CHRU Lille - Hôpital Fontan 1

Lille, , France

CHU Nantes

Nantes, , France

Hôpital Universitaire Pitié-Salpêtrière

Paris, , France

Hopital Sainte Anne

Paris, , France

Hôpital Robert Debré

Paris, , France

Vadaskert Gyermek es Ifjusagpszichiatriai Korhaz es Szakambulancia

Budapest, , Hungary

Szegedi Tudomanyegyetem

Szeged, , Hungary

Azienda Ospedaliera G. Brotzu

Cagliari, , Italy

OSP RIUNITI-DIP Donna- Bambino

Foggia, , Italy

Ospedale di Merano

Merano, , Italy

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, , Italy

Azienda Ospedaliera Universitaria Federico II

Napoli, , Italy

IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione

Pavia, , Italy

Irccs Burlo-Garofalo

Trieste, , Italy

Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ

Krakow, , Poland

Dzieciecy Szpital Kliniczny im Jozefa Polikarpa Brudzinskiego

Warsaw, , Poland

Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy

Warsaw, , Poland

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp. Sant Joan de Deu

Esplugues de Llobregat, , Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Hosp. Infantil Univ. Nino Jesus

Madrid, , Spain

Hosp. Univ. Pta. de Hierro Majadahonda

Majadahonda, , Spain

Hosp. Univ. Central de Asturias

Oviedo, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Countries

United States; Belgium; Brazil; Bulgaria; France; Hungary; Italy; Poland; Spain

References

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. 2025 Mar 7:S0890-8567(25)00122-4. doi: 10.1016/j.jaac.2025.02.015. Online ahead of print.

Reference Type: DERIVED

PMID: 40058488 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004422-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ESKETINSUI2002

Identifier Type: OTHER

Identifier Source: secondary_id

CR108323

Identifier Type: -

Identifier Source: org_study_id