Clinical trial NCT03185819: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-06-14
Enrollment: 147
Sex: ALL
Minimum age (years): 9
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at 24 Hours Post First Dose (Day 2)
timeFrame: Baseline (predose on Day 1) and 24 hours post first dose on Day 1 (i.e., Day 2)
Secondary outcomes:
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Institute of Living/ Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Atlanta Behavioral Research, LLC
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Winfield
country: United States
facility: Neuroscience Research Institute
state: Illinois
city: South Bend
country: United States
facility: Beacon Medical Group Clinical Research
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa, Carver College of Medicine
state: Iowa
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Baltimore
country: United States
facility: Sheppard Pratt Health System
state: Maryland
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Buffalo
country: United States
facility: State University of New York at Buffalo
state: New York
city: Chapel Hill
country: United States
facility: University North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Brussels
country: Belgium
facility: Hopital Erasme
city: Curitiba
country: Brazil
facility: Trial Tech Tecnologia em Pesquisas com Medicamentos
city: Salvador
country: Brazil
facility: Hospital Universitario Professor Edgar Santos
city: Sao Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
city: Turvo
country: Brazil
facility: Hospital São Sebastião
city: Ruse
country: Bulgaria
facility: Mental Health Center - Rousse
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD
city: Bron
country: France
facility: Hospices Civils de Lyon HCL
city: Lille
country: France
facility: CHRU Lille - Hôpital Fontan 1
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Hôpital Universitaire Pitié-Salpêtrière
city: Paris
country: France
facility: Hopital Sainte Anne
city: Paris
country: France
facility: Hôpital Robert Debré
city: Budapest
country: Hungary
facility: Vadaskert Gyermek es Ifjusagpszichiatriai Korhaz es Szakambulancia
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem
city: Cagliari
country: Italy
facility: Azienda Ospedaliera G. Brotzu
city: Foggia
country: Italy
facility: OSP RIUNITI-DIP Donna- Bambino
city: Merano
country: Italy
facility: Ospedale di Merano
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Pavia
country: Italy
facility: IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione
city: Trieste
country: Italy
facility: Irccs Burlo-Garofalo
city: Krakow
country: Poland
facility: Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ
city: Warszawa
country: Poland
facility: Dzieciecy Szpital Kliniczny im Jozefa Polikarpa Brudzinskiego
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Esplugues de Llobregat
country: Spain
facility: Hosp. Sant Joan de Deu
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Infantil Univ. Nino Jesus
city: Majadahonda
country: Spain
facility: Hosp. Univ. Pta. de Hierro Majadahonda
city: Oviedo
country: Spain
facility: Hosp. Univ. Central de Asturias
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: