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

A Double-blind, Randomized, Psychoactive Placebo-controlled, Study to Evaluate the Efficacy and Safety of 3 Fixed Doses (28 mg, 56 mg and 84 mg) 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 Subjects Assessed to be at Imminent Risk for Suicide

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Intranasal Placebo; Drug: Midazolam; Drug: Midazolam Placebo Solution; Drug: Esketamine; Drug: Esketamine; Drug: Esketamine

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.

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme
• Brazil
  • Curitiba, Brazil, 80240-280
    • Trial Tech Tecnologia em Pesquisas com Medicamentos
  • Salvador, Brazil, 40110-060
    • Hospital Universitario Professor Edgar Santos
  • Sao Bernardo do Campo, Brazil, 09715-090
    • CEMEC - Centro Multidisciplinar de Estudos Clínicos
  • Turvo, Brazil, 88930-000
    • Hospital São Sebastião
• Bulgaria
  • Ruse, Bulgaria, 7003
    • Mental Health Center - Rousse
  • Varna, Bulgaria
    • Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD
• France
  • Bron, France, 69677
    • Hospices Civils de Lyon HCL
  • Lille, France, 59000
    • CHRU Lille - Hôpital Fontan 1
  • Nantes, France, 44093
    • CHU Nantes
  • Paris, France, 75019
    • Hopital Robert Debre
  • Paris, France, 75013
    • Hôpital Universitaire Pitié-Salpêtrière
  • Paris, France, 75014
    • Hopital Sainte Anne
• Hungary
  • Budapest, Hungary
    • Vadaskert Gyermek- es Ifjusagpszichiatriai Korhaz es Szakambulancia
  • Szeged, Hungary
    • Szegedi Tudomanyegyetem
• Italy
  • Cagliari, Italy, 09134
    • Azienda Ospedaliera G. Brotzu
  • Foggia, Italy, 71122
    • OSP RIUNITI-DIP Donna- Bambino
  • Merano, Italy, 39012
    • Ospedale di Merano
  • Messina, Italy, 98125
    • Azienda Ospedaliera Universitaria Policlinico G. Martino
  • Napoli, Italy, 80138
    • Azienda Ospedaliera Universitaria Federico II
  • Pavia, Italy, 27100
    • IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione
  • Trieste, Italy, 34137
    • Irccs Burlo-Garofalo
• Poland
  • Krakow, Poland, 31-501
    • Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ
  • Warszawa, Poland, 02-091
    • Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego
  • Warszawa, Poland, 02-957
    • Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy
• Spain
  • Barcelona, Spain, 08036
    • Hosp. Clinic de Barcelona
  • Esplugues de Llobregat, Spain, 08950
    • Hosp. Sant Joan de Deu
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
  • Madrid, Spain, 28009
    • Hosp. Infantil Univ. Nino Jesus
  • Majadahonda, Spain, 28222
    • Hosp. Univ. Pta. de Hierro Majadahonda
  • Oviedo, Spain, 33011
    • Hosp. Univ. Central de Asturias
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Sabadell, Spain, 08208
    • Corporacio Sanitari Parc Tauli
• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Institute of Living/ Hartford Hospital
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30338
      • Atlanta Behavioral Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Winfield, Illinois, United States, 60190
      • Neuroscience Research Institute
  • Indiana
    • South Bend, Indiana, United States, 46617
      • Beacon Medical Group Clinical Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa, Carver College of Medicine
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Sheppard Pratt Health System
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health
  • New York
    • Buffalo, New York, United States, 14215
      • State University of New York at Buffalo
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University North Carolina at Chapel Hill
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Hospital
    • Cleveland, Ohio, United States, 44106
      • University Hospital of Cleveland
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9063
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Intranasal Placebo; Participants will receive placebo as intranasal dose to match intranasal esketamine.; Drug: Midazolam; Participants will receive midazolam solution 0.125 mg/kg as oral dose to match placebo.
Experimental: 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.	Drug: Midazolam Placebo Solution; Participants will receive placebo as oral dose to match midazolam drug.; Drug: Esketamine; Participants will receive esketamine at a dose of 28 mg as intranasal solution.; Drug: Esketamine; Participants will receive esketamine at a dose of 56 mg as intranasal solution.; Drug: Esketamine; Participants will receive esketamine at a dose of 84 mg as intranasal solution.
Experimental: 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.	Drug: Midazolam Placebo Solution; Participants will receive placebo as oral dose to match midazolam drug.; Drug: Esketamine; Participants will receive esketamine at a dose of 28 mg as intranasal solution.; Drug: Esketamine; Participants will receive esketamine at a dose of 56 mg as intranasal solution.; Drug: Esketamine; Participants will receive esketamine at a dose of 84 mg as intranasal solution.
Experimental: 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.	Drug: Midazolam Placebo Solution; Participants will receive placebo as oral dose to match midazolam drug.; Drug: Esketamine; Participants will receive esketamine at a dose of 28 mg as intranasal solution.; Drug: Esketamine; Participants will receive esketamine at a dose of 56 mg as intranasal solution.; Drug: Esketamine; Participants will receive esketamine at a dose of 84 mg as intranasal solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2017
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 12, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: March 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Self-Injurious Behavior; Depression; Depressive Disorder; Suicide; Suicidal Ideation; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam; Esketamine
• Other Study ID Numbers: CR108323; 2016-004422-42 (EudraCT Number); ESKETINSUI2002 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No