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NCT Number: NCT06559306

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

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).

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Key information

Conditions

Depressive Disorder, Major Depressive Disorder Mental Disorders Mood Disorders

Age range

18 year–74 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Seltorexant

Drug

Seltorexant will be administered orally.

Other names: JNJ 42847922

Placebo

Drug

Matching Placebo tablets will be administered orally.

Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Drug

SSRI/SNRI will be administered orally.

Primary outcomes

  1. Part 1: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 43

    Time frame: 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.

  2. Part 2: Time from Randomization to the First Relapse in Participants Who Achieve a Stable Response

    Time frame: 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.

Secondary outcomes

  1. Part 1: Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score at Day 43

    Time frame: Baseline, 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.

  2. 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

    Time frame: Baseline, 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.

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

    Time frame: Baseline, 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).

  4. 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

    Time frame: From Baseline to Day 43

    Responders are defined as participants with >= 50 percent improvement in the MADRS total score from baseline to Day 43.

  5. 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

    Time frame: Baseline, 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.

  6. 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

    Time frame: Baseline, 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.

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

    Time frame: Baseline, 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.

  8. Part 2: Time from Randomization to the First Relapse in Participants Who Achieve a Stable Remission

    Time frame: Time 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.

  9. Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in Sleep Disturbance Using the PROMIS-SD Short Form (8a) T-Score

    Time frame: From 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.

  10. Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in Sleep Disturbance Using the PROMIS-SD Short Form (4a) T-Score

    Time frame: From 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.

  11. 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

    Time frame: Baseline, 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.

  12. Part 2: Change from Baseline to Endpoint of the DB Maintenance Phase in MADRS Total Score

    Time frame: From 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.

  13. Part 2: Change from Baseline to Endpoint of DB Maintenance Phase in PHQ-9 Score

    Time frame: From 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.

  14. Change From Baseline to Endpoint of the DB Maintenance Phase in the MADRS-6 score

    Time frame: From 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).

  15. Change from Baseline to Endpoint of the DB Maintenance Phase in the MADRS symptoms other than insomnia MADRS Without Sleep Item (MADRS-WOSI)

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Study Contact

CONTACT

[email protected]

844-434-4210

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Aug 19, 2024
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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