A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder

Official title

A Double-blind, Randomized, Psychoactive Placebo-controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine 84 mg in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder in Adolescent Participants With Acute Suicidal Ideation or Behavior

Overview

The purpose of this study is to evaluate how well JNJ-54135419 works (efficacy) in addition to comprehensive standard of care (SoC) in rapidly reducing the symptoms of major depressive disorder (MDD, a mental disorder characterized by a persistent feeling of sadness and loss of interest in activities) as compared with psychoactive placebo (does not contain JNJ-54135419) plus SoC in adolescent participants with acute suicidal ideation or behavior.

Interventions

• Drug Esketamine
  Esketamine will be administered as intranasal solution.
• Drug Midazolam
  Midazolam will be administered as oral solution.
• Other Oral Placebo
  Placebo will be administered as oral solution.
• Other Intranasal Placebo
  Intranasal placebo will be administered as nasal solution.

Primary outcome measures

• Change from Baseline in Depressive Symptoms Measured by Children's Depression Rating Scale - Revised (CDRS-R) Total Score at 24 Hours Post First Dose [Time frame: Baseline (pre-dose on Day 1) and 24 hours post first dose (i.e., Day 2)]

Secondary outcome measures (12)

• Change from Baseline in CDRS-R Total Score at Day 25 [Time frame: Baseline (predose on Day 1) and Day 25 (4 hours post dose)]
• Change from Baseline in Clinical Global Impression - Severity of Suicidality - Revised (CGI-SS-R) Score at 24 Hours Post First Dose [Time frame: Baseline (pre-dose on Day 1) and 24 hours post first dose (i.e., Day 2)]
• Change From Baseline in Symptoms of MDD During the Double-Blind (DB) Treatment Phase as Measured by CDRS-R Total Score [Time frame: From Baseline up to Day 25]
• Percentage of Participants with Remission of Depressive Symptoms During the DB Treatment Phase [Time frame: Up to Day 25]
• Percentage of Responders on Depressive Symptoms During the DB Treatment Phase [Time frame: Up to Day 25]
• Percentage of Participants with Resolution of Suicidality During the DB Treatment Phase [Time frame: Up to Day 25]
• Change From Baseline in Severity of Suicidality As Measured by Clinical Global Impression - Severity of Suicidality - Revised (CGI-SS-R) During the DB Treatment Phase [Time frame: From Baseline up to Day 25]
• Change From Baseline in Clinician-Reported Frequency of Suicidal Thinking (FoST-ClinRO) During the DB Treatment Phase [Time frame: From Baseline up to Day 25]
• Change from baseline in Patient-Reported Frequency of Suicidal Thinking (FoST-PRO) During the DB Treatment Phase [Time frame: From Baseline up to Day 25]
• Change from Baseline in Patient Health Questionnaire, 9-item Modified for Adolescents (PHQ-A) Total Score During the DB Treatment Phase [Time frame: From Baseline up to Day 25]
• Change From Baseline in KIDSCREEN-10 Total Score During the DB Treatment Phase [Time frame: From Baseline up to Day 25]
• Change from Baseline in Patient Global Impression of Severity (PGI-S) Depressive Symptoms at 24 Hours Post First Dose [Time frame: Baseline (predose on Day 1) and 24 hours post first dose (i.e., Day 2)]

Eligibility criteria

Inclusion criteria

• Must meet diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnostic criteria for major depressive disorder (MDD) based upon clinical assessment and confirmed by the mini-international neuropsychiatric interview for children and adolescents (MINI-KID)
• Must have a clinical global impression - severity of suicidality - revised (CGI-SS-R) score of "Markedly" or greater (that is, greater than or equal to \[>=\] 4) at both screening and baseline (predose) visits
• Must have a children's depression rating scale - revised (CDRS-R) total score >= 58 at baseline (predose)
• In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to subject's acute suicidality
• Must be medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening

Exclusion criteria

• Participant has a current DSM-5 diagnosis of bipolar (or related disorders), intellectual disability, autism spectrum disorder, conduct disorder, oppositional defiant disorder
• Participant currently meets DSM-5 criteria for borderline personality disorder
• Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychosis
• Participant has a history of seizure disorder
• Participant has known allergies, hypersensitivity, intolerance or contraindications to midazolam, esketamine or ketamine, or their excipients

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 8 centers

• University of Alabama at Birmingham — Birmingham
• Children's National Medical Center — Washington D.C.
• Peachford Hospital-Atlanta Behavioral Research — Atlanta
• Endeavor Health Evanston Hospital — Evanston
• Mayo Clinic — Rochester
• University of Cincinnati — Cincinnati
• Bradley Hospital — East Providence
• John S Dunn Behavioral Sciences Center at UTHealth Houston — Houston

Spain · 7 centers

• Hosp Univ Vall D Hebron — Barcelona
• Hosp. Clinic de Barcelona — Barcelona
• Hosp. Sant Joan de Deu — Esplugues de Llobregat
• Fundacio Althaia Xarxa Assistencial Universitaria de Manresa — Manresa
• Hosp. Univ. Central de Asturias — Oviedo
• Clinica Univ. de Navarra — Pamplona
• Hosp.Univ.Parc Tauli — Sabadell

Italy · 6 centers

• Presidio Ospedaliero Santa Marta e Santa Venera — Acireale
• Azienda Ospedaliera G. Brotzu — Cagliari
• AOU Meyer — Florence
• Azienda Ospedaliera Universitaria Policlinico Riuniti di Foggia — Foggia
• Azienda Ospedaliera Universitaria Federico II — Naples
• Azienda Ospedaliero Universitaria di Sassari — Sassari

Brazil · 5 centers

• Sociedade Literaria e Caritativa Santo Agostinho Hospital Sao Jose — Criciúma
• Instituto Apice — Salvador
• Centro Integrado Facili — São Bernardo do Campo
• Instituto de Pesquisa Pensi Sandra Mutarelli Setubal — São Paulo
• Fundacao Faculdade de Medicina Hospital da Clinicas da Faculdade de Medicina de Sao Paulo — São Paulo

Taiwan · 5 centers

• Mackay Memorial Hospital Tamsui Branch — New Taipei City
• National Taiwan University Hospital — Taipei
• Taipei Medical University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei
• Tri-Service General Hospital — Taipei

Hungary · 3 centers

• Debreceni Egyetem Klinikai Kozpont — Debrecen
• Petz Aladar Megyei Oktato Korhaz — Győr
• Szegedi Tudomanyegyetem — Szeged

Romania · 1 center

• Spitalul Clinic de Urgenta pentru Copii Cluj Napoca — Cluj-Napoca

Identifiers

NCT: NCT07227454 · 54135419SUI3003 · 54135419SUI3003 · 2024-518615-19-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗