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Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms

Phase 3
Recruiting
Conditions
Depressive Disorder, Major
Interventions
Drug: Placebo
Drug: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
Registration Number
NCT06559306
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
752
Inclusion Criteria

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
Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part 1: PlaceboPlaceboParticipants 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.
Part 1: PlaceboSelective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)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.
Part 2: Open Label (OL) SeltorexantSelective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)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.
Part 1: SeltorexantSelective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)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.
Part 2: DB SeltorexantSeltorexantAll 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.
Part 2: DB SeltorexantSelective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)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.
Part 2: DB PlaceboPlaceboAll 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.
Part 2: DB PlaceboSelective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)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.
Part 2: Open Label (OL) SeltorexantSeltorexantAll 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.
Part 1: SeltorexantSeltorexantParticipants 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.
Primary Outcome Measures
NameTimeMethod
Part 1: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 43Baseline, 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 ResponseTime 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.

Secondary Outcome Measures
NameTimeMethod
Part 1: Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score at Day 43Baseline, Day 43

MADRS-WOSI considered 9 of the 10 MADRS items, excluding "reduced sleep" item. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity.

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 43Baseline, Day 43

The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 8-item form, the lowest possible raw score is 8; the highest possible raw score is 40. Higher overall score indicates more sleep disturbance.

Part 1: Change from Baseline in the MADRS-6 Total Score at Day 43Baseline, Day 43

The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of major depressive disorder (MDD) symptoms. The MADRS-6 scale is a subset of the MADRS -10 scale, comprised of the following individual questionnaire items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).

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 43From Baseline to Day 43

Responders are defined as participants with \>= 50 percent improvement in the MADRS total score 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 43Baseline, Day 43

The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 4-item short form will be used in this study, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 4-item form, the lowest possible raw score is 4; the highest possible raw score is 20. Higher overall score indicates more sleep disturbance.

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 43Baseline, Day 43

The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 10-item short form will be used, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 10-item form, the lowest possible raw score is 10; the highest possible raw score is 50. Higher overall score indicates more sleep disturbance.

Part 1: Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score at Day 43Baseline, Day 43

The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the diagnostic and statistical manual of mental disorders-5th edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.

Part 2: Time from Randomization to the First Relapse in Participants Who Achieve a Stable RemissionTime from randomization to the first relapse during the maintenance phase (up to 2 years and 10 months)

Stable remission is defined as MADRS total score less than or equal to (\<=)10 and CGI-S \<= 2 for at least 4 consecutive weeks of the OL stabilization Phase. Time from randomization to the first relapse during the DB maintenance phase in participants who achieve stable remission at the end of the OL seltorexant treatment will be reported.

Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in Sleep Disturbance Using the PROMIS-SD Short Form (8a) T-ScoreFrom Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337)

The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 8-item form, the lowest possible raw score is 8; the highest possible raw score is 40. Higher overall score indicates more sleep disturbance.

Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in Sleep Disturbance Using the PROMIS-SD Short Form (4a) T-ScoreFrom Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337)

The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 4-item short form will be used in this study, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 4-item form, the lowest possible raw score is 4; the highest possible raw score is 20. Higher overall score indicates more sleep disturbance.

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 43Baseline, Day 43

The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 10-item short form will be used, in which responses are scored 1 to 5 for each item. T-score for the PROMIS-SD scales represent the value obtained after using a conversion table to convert the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 10-item form, the lowest possible raw score is 10; the highest possible raw score is 50. Higher overall score indicates more sleep disturbance.

Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in MADRS Total ScoreFrom Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337)

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: Change from Baseline to Endpoint of DB Maintenance Phase in PHQ-9 ScoreFrom Baseline (Day 1 in the DB Treatment Maintenance Phase) Until End Point of the DB Maintenance Phase (that is, up to Day 337)

The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the DSM-5 MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.

Change From Baseline to Endpoint of the DB Maintenance Phase in the MADRS-6 scoreFrom Baseline (Day 1 in the DB treatment maintenance Phase) until end point of the DB maintenance phase (that is up to Day 337)

The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS -10 scale, comprised of the following individual questionnaire items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).

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)

MADRS-WOSI considered 9 of the 10 MADRS items, excluding "reduced sleep" item. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity.

Trial Locations

Locations (186)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Chandler Clinical Trials

🇺🇸

Chandler, Arizona, United States

University of Arizona

🇺🇸

Tucson, Arizona, United States

SanRo Clinical Research Group LLC WCG Clinical Network

🇺🇸

Bryant, Arkansas, United States

Preferred Research Partners

🇺🇸

Little Rock, Arkansas, United States

PAMOJA Clinical Institute LLC

🇺🇸

Anaheim, California, United States

Axiom Research

🇺🇸

Colton, California, United States

Elite Research Network

🇺🇸

Encino, California, United States

Behavioral Research Specialists LLC

🇺🇸

Glendale, California, United States

WR PRI Los Alamitos

🇺🇸

Los Alamitos, California, United States

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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States

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