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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 258
- 试验地点
- 40
- 主要终点
- Change from Baseline in Depressive Symptoms Measured by Children's Depression Rating Scale - Revised (CDRS-R) Total Score at 24 Hours Post First Dose
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Intranasal Placebo + Oral Midazolam
Participants will receive oral midazolam (0.0625 milligrams per kilograms [mg/kg]) and intranasal placebo twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a sham decrease to esketamine 56 mg dose (in a blinded fashion per investigator's judgment) is permitted. Thereafter, sham dose may be flexed between 56 mg and 84 mg during the treatment period.
干预措施: Midazolam (Drug)
Intranasal Esketamine + Oral Placebo
Participants will receive intranasal esketamine 84 milligrams (mg) along with oral placebo solution twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a decrease to intranasal esketamine 56 mg (in a blinded fashion per investigator's judgment) is permitted. Thereafter, dose may be flexed between 56 mg and 84 mg during the treatment period.
干预措施: Oral Placebo (Other)
Intranasal Placebo + Oral Midazolam
Participants will receive oral midazolam (0.0625 milligrams per kilograms [mg/kg]) and intranasal placebo twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a sham decrease to esketamine 56 mg dose (in a blinded fashion per investigator's judgment) is permitted. Thereafter, sham dose may be flexed between 56 mg and 84 mg during the treatment period.
干预措施: Intranasal Placebo (Other)
Intranasal Esketamine + Oral Placebo
Participants will receive intranasal esketamine 84 milligrams (mg) along with oral placebo solution twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a decrease to intranasal esketamine 56 mg (in a blinded fashion per investigator's judgment) is permitted. Thereafter, dose may be flexed between 56 mg and 84 mg during the treatment period.
干预措施: Esketamine (Drug)
结局指标
主要结局
Change from Baseline in Depressive Symptoms Measured by Children's Depression Rating Scale - Revised (CDRS-R) Total Score at 24 Hours Post First Dose
时间窗: Baseline (pre-dose on Day 1) and 24 hours post first dose (i.e., Day 2)
The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive symptom severity. Out 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.
次要结局
- Change from Baseline in CDRS-R Total Score at Day 25(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(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(From Baseline up to Day 25)
- Percentage of Participants with Remission of Depressive Symptoms During the DB Treatment Phase(Up to Day 25)
- Percentage of Responders on Depressive Symptoms During the DB Treatment Phase(Up to Day 25)
- Percentage of Participants with Resolution of Suicidality During the DB Treatment Phase(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(From Baseline up to Day 25)
- Change From Baseline in Clinician-Reported Frequency of Suicidal Thinking (FoST-ClinRO) During the DB Treatment Phase(From Baseline up to Day 25)
- Change from baseline in Patient-Reported Frequency of Suicidal Thinking (FoST-PRO) During the DB Treatment Phase(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(From Baseline up to Day 25)
- Change From Baseline in KIDSCREEN-10 Total Score During the DB Treatment Phase(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(Baseline (predose on Day 1) and 24 hours post first dose (i.e., Day 2))
- Change from Baseline in Clinical Global Impression - Severity Scale (CGI-S) Depressive Symptoms at 24 Hours Post First Dose(Baseline (pre-dose on Day 1) and 24 hours post first dose (i.e., Day 2))