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

Depressive Disorder, Major Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03185819
• Other study ID #: CR108323
• Secondary ID: 2016-004422-42ES
• Status: Completed
• Phase: Phase 2
• Start date: October 5, 2017
• Est. completion date: March 31, 2023

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Suicidal Ideation
• Suicide

Intervention

Drug:
• Intranasal Placebo
Participants will receive placebo as intranasal dose to match intranasal esketamine.
• Midazolam Placebo Solution
Participants will receive placebo as oral dose to match midazolam drug.
• Midazolam
Participants will receive midazolam solution 0.125 mg/kg as oral dose to match placebo.
• Esketamine
Participants will receive esketamine at a dose of 28 mg as intranasal solution.
• Esketamine
Participants will receive esketamine at a dose of 56 mg as intranasal solution.
• Esketamine
Participants will receive esketamine at a dose of 84 mg as intranasal solution.

Locations

Country	Name	City	State
Belgium	Hopital Erasme	Brussels
Brazil	Trial Tech Tecnologia em Pesquisas com Medicamentos	Curitiba
Brazil	Hospital Universitario Professor Edgar Santos	Salvador
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	Sao Bernardo do Campo
Brazil	Hospital São Sebastião	Turvo
Bulgaria	Mental Health Center - Rousse	Ruse
Bulgaria	Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD	Varna
France	Hospices Civils de Lyon HCL	Bron
France	CHRU Lille - Hôpital Fontan 1	Lille
France	CHU Nantes	Nantes
France	Hôpital Robert Debré	Paris
France	Hopital Sainte Anne	Paris
France	Hôpital Universitaire Pitié-Salpêtrière	Paris
Hungary	Vadaskert Gyermek- és Ifjúságpszichiátriai Kórház és Szakambulancia	Budapest
Hungary	Szegedi Tudomanyegyetem	Szeged
Italy	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
Poland	Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ	Krakow
Poland	Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego	Warszawa
Poland	Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy	Warszawa
Spain	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
United States	Atlanta Behavioral Research, LLC	Atlanta	Georgia
United States	Sheppard Pratt Health System	Baltimore	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	Rush University Medical Center	Chicago	Illinois
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	University of Texas Southwestern Medical Center	Dallas	Texas
United States	CBH Health	Gaithersburg	Maryland
United States	Institute of Living/ Hartford Hospital	Hartford	Connecticut
United States	University of Iowa, Carver College of Medicine	Iowa City	Iowa
United States	Lake Charles Clinical Trials	Lake Charles	Louisiana
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Beacon Medical Group Clinical Research	South Bend	Indiana
United States	Neuroscience Research Institute	Winfield	Illinois
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)