A Two-Part Multicenter, Double-Blind, Randomized Placebo-Controlled Study to Evaluate Efficacy and Safety and the Maintenance of Effect of 20-(Milligram) mg Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients With Major Depressive Disorder With Insomnia Symptoms
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 752
- 试验地点
- 407
- 主要终点
- Part 1: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 43
研究概览
简要总结
The purpose of this study is to know how well seltorexant works, and also to evaluate safety and maintenance effect of seltorexant compared with placebo as an adjunctive therapy to an antidepressant in improving depressive symptoms in participants with major depressive disorder with insomnia symptoms (MDDIS) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
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 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants in part 1 and direct enrollers to part 2:
- •Meet DSM-5 MDD, without psychotic features based upon clinical assessment and confirmed by the structured clinical interview for DSM-5 Axis I disorders-clinical trials version (SCID-CT) diagnosed with first depressive episode prior to age 60
- •Have had an inadequate response to at least 1 but no more than 2 antidepressants, administered at an adequate dose and duration in the current episode of depression. An inadequate response is defined as less than (<) 50% reduction but with some improvement (that is, improvement greater than [>] 0%) in depressive symptom severity with residual symptoms other than insomnia present, and overall good tolerability, as assessed by the MGH-ATRQ, and this must include the participant's current antidepressant treatment
- •Is receiving and tolerating well any one of the following SSRI or SNRI for depressive symptoms at screening, in any formulation and available in the participating country: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at therapeutic dose level) for at least 6 weeks
- •Having a major depressive episode of at least moderate severity, as assessed with 17-item Hamilton Depression Rating Scale, implemented through the Structured Interview Guide (SIGH-D) in a blinded manner at screening and must not demonstrate a clinically significant improvement from the beginning to end of screening.
- •Participants entering after completing part 1:
- •Must have completed Part 1 DB treatment phase
- •Can consistently tolerate study drug (at the end of Part 1), and there is no additional safety risk for the participant if they proceed to Part 2
- •Was able to consistently follow the study procedures in Part 1 as judged by the investigator.
- •Must be medically stable based on clinical laboratory tests
排除标准
- •Has a recent (last 3 months) history of, or current signs and symptoms of, severe renal insufficiency clinically significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders and uncontrolled Type 1 or Type 2 diabetes mellitus
- •Has a history of narcolepsy and seizures
- •Has current signs/symptoms of hypothyroidism or hyperthyroidism
- •Participants taking thyroid supplementation for antidepressant purposes
- •Has Cushing's disease, Addison's disease, primary amenorrhea, or other evidence of significant medical disorders of the HPA axis
研究组 & 干预措施
Part 2: DB Placebo
All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. Participants who achieve a stable response during the open-label phases will receive treatment with matching placebo orally once daily during DB Maintenance Phase in Part 2 of the study. Participants will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.
干预措施: Placebo (Drug)
Part 1: Seltorexant
Participants will receive seltorexant orally once daily for 6 weeks during the double-blind (DB) treatment phase in Part 1 of the study. Participants who do not proceed to Part 2 of the study will undergo a post-treatment follow-up phase, after the DB treatment phase in Part 1 and will continue to take their single baseline selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant throughout the study.
干预措施: Seltorexant (Drug)
Part 2: DB Seltorexant
All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. Participants who achieve a stable response during the open-label phase will receive treatment with seltorexant orally once daily during DB Maintenance Phase in Part 2 of the study. Participants will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.
干预措施: Seltorexant (Drug)
Part 2: Open Label (OL) Seltorexant
All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. In Part 2 open-label phases (induction and stabilization) all participants (newly enrolled direct entry participants and Part 1 roll-over participants) will receive seltorexant orally in addition to their background SSRI/SNRI treatment.
干预措施: Seltorexant (Drug)
Part 1: Placebo
Participants will receive matching placebo orally once daily for 6 weeks during the DB treatment phase in Part 1 of the study. Participants who do not proceed to Part 2 of the study will undergo a post-treatment follow-up phase, after the DB treatment phase in Part 1 and will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.
干预措施: Placebo (Drug)
Part 2: DB Seltorexant
All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. Participants who achieve a stable response during the open-label phase will receive treatment with seltorexant orally once daily during DB Maintenance Phase in Part 2 of the study. Participants will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) (Drug)
Part 1: Seltorexant
Participants will receive seltorexant orally once daily for 6 weeks during the double-blind (DB) treatment phase in Part 1 of the study. Participants who do not proceed to Part 2 of the study will undergo a post-treatment follow-up phase, after the DB treatment phase in Part 1 and will continue to take their single baseline selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant throughout the study.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) (Drug)
Part 1: Placebo
Participants will receive matching placebo orally once daily for 6 weeks during the DB treatment phase in Part 1 of the study. Participants who do not proceed to Part 2 of the study will undergo a post-treatment follow-up phase, after the DB treatment phase in Part 1 and will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) (Drug)
Part 2: Open Label (OL) Seltorexant
All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. In Part 2 open-label phases (induction and stabilization) all participants (newly enrolled direct entry participants and Part 1 roll-over participants) will receive seltorexant orally in addition to their background SSRI/SNRI treatment.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) (Drug)
Part 2: DB Placebo
All participants who complete Part 1, and who meet eligibility criteria for Part 2, as well as direct entry participants, will enter Part 2 of the study. Participants who achieve a stable response during the open-label phases will receive treatment with matching placebo orally once daily during DB Maintenance Phase in Part 2 of the study. Participants will continue to take their single baseline SSRI/SNRI antidepressant throughout the study.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) (Drug)
结局指标
主要结局
Part 1: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 43
时间窗: Baseline, Day 43
The MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Part 2: Time from Randomization to the First Relapse in Participants Who Achieve a Stable Response
时间窗: Time from randomization to the first Relapse during the maintenance phase (up to 2 years and 10 months)
Stable response is defined as a greater than equal to (\>=) 50 percent (%) reduction in the MADRS total score for the last 3 consecutive visits of the OL stabilization Phase, as assessed by the site investigator. Time from randomization to the first relapse during the DB maintenance phase in participants who achieve a stable response at the end of OL seltorexant treatment will be reported.
次要结局
- Part 1: Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score at Day 43(Baseline, Day 43)
- Part 1: Change from Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a T-score at Day 43(Baseline, Day 43)
- Part 1: Change from Baseline in the MADRS-6 Total Score at Day 43(Baseline, Day 43)
- Part 1: Percentage of Participants with Response on Depressive Symptoms Scale Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total score From Baseline to Day 43(From Baseline to Day 43)
- Part 1: Change from Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form (4a) T-score at Day 43(Baseline, Day 43)
- Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in MADRS Total Score(From Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337))
- Part 1: Change from Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form (10a) T-score at Day 43(Baseline, Day 43)
- Part 1: Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score at Day 43(Baseline, Day 43)
- Part 2: Time from Randomization to the First Relapse in Participants Who Achieve a Stable Remission(Time from randomization to the first relapse during the maintenance phase (up to 2 years and 10 months))
- Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in Sleep Disturbance Using the PROMIS-SD Short Form (8a) T-Score(From Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337))
- Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in Sleep Disturbance Using the PROMIS-SD Short Form (4a) T-Score(From Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337))
- Part 2: Change from Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form (10a) T-score at Day 43(Baseline, Day 43)
- Part 2: Change from Baseline to Endpoint of DB Maintenance Phase in PHQ-9 Score(From Baseline (Day 1 in the DB Treatment Maintenance Phase) Until End Point of the DB Maintenance Phase (that is, up to Day 337))
- Change From Baseline to Endpoint of the DB Maintenance Phase in the MADRS-6 score(From Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337))
- Change from Baseline to Endpoint of the DB Maintenance Phase in the MADRS symptoms other than insomnia MADRS Without Sleep Item (MADRS-WOSI)(From Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337))