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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

Primary Purpose

Depressive Disorder, Major

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Intranasal Placebo
Midazolam Placebo Solution
Midazolam
Esketamine
Esketamine
Esketamine
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depressive Disorder, Major

Eligibility Criteria

9 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institute of Living/ Hartford Hospital
  • Yale University
  • Atlanta Behavioral Research, LLC
  • Rush University Medical Center
  • Neuroscience Research Institute
  • Beacon Medical Group Clinical Research
  • University of Iowa, Carver College of Medicine
  • Lake Charles Clinical Trials
  • Sheppard Pratt Health System
  • CBH Health
  • State University of New York at Buffalo
  • University North Carolina at Chapel Hill
  • Wake Forest Baptist Medical Center
  • University of Cincinnati Hospital
  • University Hospital of Cleveland
  • Ohio State University
  • Vanderbilt University Medical Center
  • University of Texas Southwestern Medical Center
  • Hopital Erasme
  • Hospital Universitario Professor Edgar Santos
  • Trial Tech Tecnologia em Pesquisas com Medicamentos
  • CEMEC - Centro Multidisciplinar de Estudos Clínicos
  • Hospital São Sebastião
  • Mental Health Center - Rousse
  • Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD
  • Hospices Civils de Lyon HCL
  • CHRU Lille - Hôpital Fontan 1
  • CHU Nantes
  • Hôpital Universitaire Pitié-Salpêtrière
  • Hopital Sainte Anne
  • Hôpital Robert Debré
  • Vadaskert Gyermek- és Ifjúságpszichiátriai Kórház és Szakambulancia
  • Szegedi Tudomanyegyetem
  • Azienda Ospedaliera G. Brotzu
  • OSP RIUNITI-DIP Donna- Bambino
  • Ospedale di Merano
  • Azienda Ospedaliera Universitaria Policlinico G. Martino
  • Azienda Ospedaliera Universitaria Federico II
  • IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione
  • Irccs Burlo-Garofalo
  • Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ
  • Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego
  • Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy
  • Hosp. Clinic I Provincial de Barcelona
  • Hosp. Sant Joan de Deu
  • Hosp. Gral. Univ. Gregorio Marañon
  • Hosp. Infantil Univ. Niño Jesus
  • Hosp. Univ. Pta. de Hierro Majadahonda
  • Hosp. Univ. Central de Asturias
  • Clinica Univ. de Navarra
  • Corporacio Sanitari Parc Tauli

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Oral Midazolam + Intranasal Placebo

Oral Placebo + Esketamine 84 mg

Oral Placebo + Esketamine 56 mg

Oral Placebo + Esketamine 28 mg

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at 24 Hours Post First Dose
The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. The highest possible score is 113 (the most severe measure of depression), and the lowest is 17 (not suffering from depression).

Secondary Outcome Measures

Full Information

First Posted
June 12, 2017
Last Updated
May 1, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03185819
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
October 5, 2017 (Actual)
Primary Completion Date
March 31, 2023 (Actual)
Study Completion Date
March 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Major

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
147 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral Midazolam + Intranasal Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Oral Placebo + Esketamine 84 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Oral Placebo + Esketamine 56 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Oral Placebo + Esketamine 28 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Intranasal Placebo
Intervention Description
Participants will receive placebo as intranasal dose to match intranasal esketamine.
Intervention Type
Drug
Intervention Name(s)
Midazolam Placebo Solution
Intervention Description
Participants will receive placebo as oral dose to match midazolam drug.
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Participants will receive midazolam solution 0.125 mg/kg as oral dose to match placebo.
Intervention Type
Drug
Intervention Name(s)
Esketamine
Intervention Description
Participants will receive esketamine at a dose of 28 mg as intranasal solution.
Intervention Type
Drug
Intervention Name(s)
Esketamine
Intervention Description
Participants will receive esketamine at a dose of 56 mg as intranasal solution.
Intervention Type
Drug
Intervention Name(s)
Esketamine
Intervention Description
Participants will receive esketamine at a dose of 84 mg as intranasal solution.
Primary Outcome Measure Information:
Title
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at 24 Hours Post First Dose
Description
The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. The highest possible score is 113 (the most severe measure of depression), and the lowest is 17 (not suffering from depression).
Time Frame
Baseline and 24 hours post-administration of first dose on Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
9 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Institute of Living/ Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Atlanta Behavioral Research, LLC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30338
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Neuroscience Research Institute
City
Winfield
State/Province
Illinois
ZIP/Postal Code
60190
Country
United States
Facility Name
Beacon Medical Group Clinical Research
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46617
Country
United States
Facility Name
University of Iowa, Carver College of Medicine
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Lake Charles Clinical Trials
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70629
Country
United States
Facility Name
Sheppard Pratt Health System
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
CBH Health
City
Gaithersburg
State/Province
Maryland
ZIP/Postal Code
20877
Country
United States
Facility Name
State University of New York at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
University North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
University of Cincinnati Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
University Hospital of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9063
Country
United States
Facility Name
Hopital Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Hospital Universitario Professor Edgar Santos
City
Bahia
ZIP/Postal Code
40110-060
Country
Brazil
Facility Name
Trial Tech Tecnologia em Pesquisas com Medicamentos
City
Curitiba
ZIP/Postal Code
80240-280
Country
Brazil
Facility Name
CEMEC - Centro Multidisciplinar de Estudos Clínicos
City
São Bernardo do Campo
ZIP/Postal Code
09715-090
Country
Brazil
Facility Name
Hospital São Sebastião
City
Turvo
ZIP/Postal Code
88930-000
Country
Brazil
Facility Name
Mental Health Center - Rousse
City
Ruse
ZIP/Postal Code
7003
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD
City
Varna
Country
Bulgaria
Facility Name
Hospices Civils de Lyon HCL
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
CHRU Lille - Hôpital Fontan 1
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
CHU Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hôpital Universitaire Pitié-Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hopital Sainte Anne
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
Hôpital Robert Debré
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Vadaskert Gyermek- és Ifjúságpszichiátriai Kórház és Szakambulancia
City
Budapest
Country
Hungary
Facility Name
Szegedi Tudomanyegyetem
City
Szeged
Country
Hungary
Facility Name
Azienda Ospedaliera G. Brotzu
City
Cagliari
ZIP/Postal Code
09134
Country
Italy
Facility Name
OSP RIUNITI-DIP Donna- Bambino
City
Foggia
ZIP/Postal Code
71122
Country
Italy
Facility Name
Ospedale di Merano
City
Merano
ZIP/Postal Code
39012
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Policlinico G. Martino
City
Messina
ZIP/Postal Code
98125
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Federico II
City
Napoli
ZIP/Postal Code
80138
Country
Italy
Facility Name
IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Irccs Burlo-Garofalo
City
Trieste
ZIP/Postal Code
34137
Country
Italy
Facility Name
Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
Facility Name
Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego
City
Warszawa
ZIP/Postal Code
02-091
Country
Poland
Facility Name
Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy
City
Warszawa
ZIP/Postal Code
02-957
Country
Poland
Facility Name
Hosp. Clinic I Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hosp. Sant Joan de Deu
City
Esplugues de Llobregat
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hosp. Gral. Univ. Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hosp. Infantil Univ. Niño Jesus
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hosp. Univ. Pta. de Hierro Majadahonda
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hosp. Univ. Central de Asturias
City
Oviedo
ZIP/Postal Code
33011
Country
Spain
Facility Name
Clinica Univ. de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Corporacio Sanitari Parc Tauli
City
Sabadell
ZIP/Postal Code
08208
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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