Clinical TrialMajor Depressive Disorder (MDD)PlaceboPlaceboEsketaminePlaceboEsketaminePlaceboEsketaminePlaceboCompleted

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

This double-blind, randomized, psychoactive placebo-controlled trial (n=147) assessed 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 rapidly reducing the symptoms of major depressive disorder (MDD), including suicidal ideation, in pediatric subjects.

Target Enrollment
147 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Randomized, double-blind, parallel-group Phase II study in paediatric participants with MDD and imminent suicide risk comparing intranasal esketamine (28, 56, 84 mg) plus standard care versus psychoactive placebo (oral midazolam) with intranasal placebo.

Primary assessments focused on rapid reduction of depressive and suicidal symptoms after dosing; safety, pharmacokinetic, biomarker, and pharmacogenomic evaluations were performed across a 25-day double-blind phase and extended follow-up to 6 months.

Study Protocol

Preparation

sessions

Dosing

3 sessions

Integration

sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

Midazolam + IN placebo

inactive

Oral midazolam 0.125 mg/kg plus intranasal placebo matching esketamine.

Interventions

  • Placebo0.125 mg/kg
    via Oral• twice weekly for 4 weeks

    Oral midazolam 0.125 mg/kg given 2x/week for 4 weeks (psychoactive placebo).

  • Placebo
    via Other• three doses

    Intranasal placebo matched to esketamine; described as 3 intranasal doses.

Esketamine 84 mg

experimental

Intranasal esketamine 84 mg plus oral placebo.

Interventions

  • Esketamine84 mg
    via Other• three doses

    84 mg delivered as 6 x 14 mg sprays (3 per nostril) as described.

  • Placebo
    via Oral• twice weekly for 4 weeks

    Oral placebo matching midazolam given 2x/week for 4 weeks.

Esketamine 56 mg

experimental

Intranasal esketamine 56 mg plus oral placebo.

Interventions

  • Esketamine56 mg
    via Other• three doses

    56 mg delivered as 4 x 14 mg sprays.

  • Placebo
    via Oral• twice weekly for 4 weeks

    Oral placebo matching midazolam.

Esketamine 28 mg

experimental

Intranasal esketamine 28 mg plus oral placebo.

Interventions

  • Esketamine28 mg
    via Other• three doses

    28 mg delivered as 2 x 14 mg sprays.

  • Placebo
    via Oral• twice weekly for 4 weeks

    Oral placebo matching midazolam.

Participants

Ages
9 – 17
Sexes
Male & Female

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 >= 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 Details

Locations

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
University of Iowa, Carver College of Medicine — Iowa City, Iowa, United States
Lake Charles Clinical Trials — Lake Charles, Louisiana, United States
Sheppard Pratt Health System — Baltimore, Maryland, United States
CBH Health — Gaithersburg, 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
Wake Forest Baptist Medical Center — Winston-Salem, North Carolina, 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
Vanderbilt University Medical Center — Nashville, Tennessee, United States
University of Texas Southwestern Medical Center — Dallas, Texas, United States
Hopital Erasme — Brussels, Belgium
Trial Tech Tecnologia em Pesquisas com Medicamentos — Curitiba, Brazil
Hospital Universitario Professor Edgar Santos — Salvador, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos — São Bernardo do Campo, Brazil
Hospital São Sebastião — Turvo, Brazil
Mental Health Center - Rousse — Rousse, Bulgaria
Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD — Varna, Bulgaria
Hospices Civils de Lyon HCL — Bron, France
CHRU Lille - Hôpital Fontan 1 — Lille, France
CHU Nantes — Nantes, France
Hôpital Universitaire Pitié-Salpêtrière — Paris, France
Hopital Sainte Anne — Paris, France
Hôpital Robert Debré — Paris, France
Vadaskert Gyermek es Ifjusagpszichiatriai Korhaz es Szakambulancia — Budapest, Hungary
Szegedi Tudomanyegyetem — Szeged, Hungary
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, Italy
Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ — Krakow, Poland
Dzieciecy Szpital Kliniczny im Jozefa Polikarpa Brudzinskiego — Warsaw, Poland
Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy — Warsaw, Poland
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, Spain

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