A Double-blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Subjects Who Are Assessed to be at Imminent Risk for Suicide
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 主要终点
- Change From Baseline to Day 1: 4-Hour Post-dose in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Double-blind Phase)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of intranasal esketamine 84 milligram (mg) compared with intranasal placebo along with standard care treatment, in reducing the symptoms of major depressive disorder (MDD) (an affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities, the mood disturbance is prominent and relatively persistent), including the risk for suicide as assessed by the Investigator, in participants who will be assessed to be at imminent risk for suicide.
详细描述
This is a randomized (study medication assigned to participants by chance), double-blind (neither physician nor participant knows assigned study treatment), placebo-controlled (participants are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug), and multicenter (when more than one hospital or medical school team works on a medical research study), study of esketamine in participants with major depressive disorder (MDD) in participants who will be assessed to be at imminent risk for suicide, as measured by the change from Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 4 hours postdose on Day 1. The duration of study will be approximately 81 days per participant. The study consists of 3 parts: Screening (that is, with in 1 day before study commences on Day 1) and double-blind Treatment (from Day 1-25) and Follow-up (from Day 26 up to Day 81). All the eligible participants will be provided standard care treatment and will be randomly assigned to either esketmaine or placebo treatment. Esketamine/placebo will be administered by intranasal route (delivery of medications through the nasal mucosa) two times per week for 4 weeks. Efficacy of the participants will be primarily evaluated through MADRS. Participants' safety will be monitored throughout the study.
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
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for major depressive disorder
- •Participants must have current suicidal ideation with intent
- •In the Investigator's opinion, participant must be in need of acute psychiatric hospitalization due to imminent risk of suicide
- •Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than or equal to (>=) 22 predose on Day 1
- •As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 5 days after randomization (that is, through Day 5), and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)
排除标准
- •Participant has a current clinical diagnosis of bipolar or related disorders, intellectual disability, or cluster b personality disorder (example, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder)
- •Participant meets DSM-IV criteria for borderline personality disorder, based on clinical interview
- •Participant has a current or prior diagnosis of a psychotic disorder, major depressive disorder (MDD) with psychosis, or obsessive compulsive disorder
- •Participant with a history or current signs and symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances
- •Participant has uncontrolled hypertension (systolic blood pressure greater than [>] 160 millimeter of mercury [mmHg] or diastolic blood pressure > 90 mmHg) despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment at Screening; or any past history of hypertensive crisis
研究组 & 干预措施
Esketamine
Esketamine hydrochloride solution (containing 14 milligram (mg) of esketamine base per 100 microliter [mcl] of intranasal spray) will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks. Dose may be reduced to 56 mg per day based on Investigator's discretion.
干预措施: Esketamine (Drug)
Placebo
Matching Placebo solution will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Day 1: 4-Hour Post-dose in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Double-blind Phase)
时间窗: Baseline (Day 1-Predose) to Day 1: 4-hours post-dose
The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The last observation carried forward (LOCF) approach was used for missing visit data in the ITT LOCF efficacy analyses.
次要结局
- Change From Baseline to Day 1: 4- Hours Postdose in SIBAT-Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 1: 4-hours postdose)
- Change From Baseline to Day 2 in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (SIBAT CGJ-SR) Module 8 Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 2)
- Change From Baseline to Double-blind Phase-Endpoint (Day 25) Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (SIBAT CGJ-SR) Module 8 (Double-blind Phase)(Baseline (Day 1-predose) to Double-blind Phase-Endpoint (Day 25))
- Change From Baseline to Day 1: 4-Hours Postdose in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 1: 4-hours postdose)
- Change From Baseline to Day 2 in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 2)
- Change From Baseline to Day 2 in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 2)
- Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Follow-up Phase)(Baseline (Day 1-predose) to Follow-up Phase Endpoint (Day 81))
- Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Scale for Suicidal Ideation Total Score (Double-blind Phase)(Baseline (Day 1-predose) to Double-blind Phase-endpoint (Day 25))
- Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Beck Scale for Suicidal Ideation Total Score (Follow-up Phase)(Baseline (Day 1-predose) to Follow-up Phase-Endpoint (Day 81))
- Percentage of Participants With Sustained Response Based on MADRS Total Score (Double-blind Phase)(Day 1 to Day 25)
- Percentage of Participants With Response Based on MADRS Total Score During the Double-Blind Phase(Day 1 (4 hours postdose), Day 2 (double blind phase), Double blind phase -Endpoint (Day 25))
- Change From Baseline to Day 2 in MADRS Total Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 2)
- Change From Baseline to Day 1: 4-hours Post-dose in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (CGJ-SR) Module 8 Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 1: 4-hours Postdose)
- Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk Score (Follow-up Phase)(Baseline (Day 1-predose) to Follow-up Phase-Endpoint (Day 81))
- Change From Baseline to Double Blind Phase-Endpoint (Day 25) in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)(Baseline (Day 1-predose) to Double-blind Phase-Endpoint (Day 25))
- Change From Baseline to Day 1: 4-Hours Postdose in Beck Hopelessness Scale (BHS) Total Score (Double-blind Phase)(Baseline (Day 1-predose) to Day 1: 4-hours Postdose)
- Change From Baseline to Double-blind Phase-End Point (Day 25) in MADRS Total Score (Double-blind Phase)(Baseline (Day 1-predose) to Double-blind Phase-End Point (Day 25))
- Percentage of Participants With Response Based on MADRS Total Score at Follow up Phase Endpoint(Follow up phase-endpoint (Day 81))
- Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Hopelessness Scale Total Score (Double-blind Phase)(Baseline (Day 1-predose) to Double-blind Phase-Endpoint (Day 25))