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
- Conditions
- Depressive Disorder, Major
- Interventions
- Registration Number
- NCT03185819
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 147
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Oral Midazolam + Intranasal Placebo 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. Oral Placebo + Esketamine 28 mg Midazolam Placebo Solution 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. Oral Placebo + Esketamine 84 mg Midazolam Placebo Solution 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. Oral Placebo + Esketamine 56 mg Midazolam Placebo Solution 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. Oral Midazolam + Intranasal Placebo Midazolam 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. Oral Placebo + Esketamine 84 mg 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. Oral Placebo + Esketamine 56 mg Esketamine 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. Oral Placebo + Esketamine 28 mg Esketamine 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at 24 Hours Post First Dose (Day 2) Baseline (predose on Day 1) and 24 hours post first dose on Day 1 (i.e., 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (51)
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Italy
OSP RIUNITI-DIP Donna- Bambino
🇮🇹Foggia, Italy
Vadaskert Gyermek es Ifjusagpszichiatriai Korhaz es Szakambulancia
🇭🇺Budapest, Hungary
Dzieciecy Szpital Kliniczny im Jozefa Polikarpa Brudzinskiego
🇵🇱Warszawa, Poland
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
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
CBH Health
🇺🇸Gaithersburg, Maryland, United States
University of Iowa, Carver College of Medicine
🇺🇸Iowa City, Iowa, United States
University North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Lake Charles Clinical Trials
🇺🇸Lake Charles, Louisiana, United States
Sheppard Pratt Health System
🇺🇸Baltimore, Maryland, United States
State University of New York at Buffalo
🇺🇸Buffalo, New York, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Hopital Erasme
🇧🇪Brussels, Belgium
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
Hospital Universitario Professor Edgar Santos
🇧🇷Salvador, Brazil
Szegedi Tudomanyegyetem
🇭🇺Szeged, Hungary
Hosp. Univ. Central de Asturias
🇪🇸Oviedo, Spain
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Trial Tech Tecnologia em Pesquisas com Medicamentos
🇧🇷Curitiba, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos
🇧🇷Sao Bernardo do Campo, Brazil
Hospital São Sebastião
🇧🇷Turvo, Brazil
CHU Nantes
🇫🇷Nantes, France
Hôpital Universitaire Pitié-Salpêtrière
🇫🇷Paris, France
Ospedale di Merano
🇮🇹Merano, Italy
Mental Health Center - Rousse
🇧🇬Ruse, Bulgaria
Hospices Civils de Lyon HCL
🇫🇷Bron, France
CHRU Lille - Hôpital Fontan 1
🇫🇷Lille, France
Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD
🇧🇬Varna, Bulgaria
Hopital Sainte Anne
🇫🇷Paris, France
Hôpital Robert Debré
🇫🇷Paris, France
Irccs Burlo-Garofalo
🇮🇹Trieste, Italy
Azienda Ospedaliera G. Brotzu
🇮🇹Cagliari, Italy
Azienda Ospedaliera Universitaria Policlinico G. Martino
🇮🇹Messina, Italy
Hosp. Sant Joan de Deu
🇪🇸Esplugues de Llobregat, Spain
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp. Univ. Pta. de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione
🇮🇹Pavia, Italy
Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ
🇵🇱Krakow, Poland
Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy
🇵🇱Warszawa, Poland
Hosp. Infantil Univ. Nino Jesus
🇪🇸Madrid, Spain
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain