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

Phase 3RecruitingNCT06559306

Janssen Research & Development, LLC752 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

752

Conditions

Depressive Disorder, Major

Interventions

Seltorexant

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

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

Locations (198)

University of Alabama at Birmingham

Birmingham, Alabama, United States

RECRUITING

Chandler Clinical Trials

Chandler, Arizona, United States

COMPLETED

University of Arizona

Tucson, Arizona, United States

RECRUITING

SanRo Clinical Research Group LLC WCG Clinical Network

Bryant, Arkansas, United States

Outcomes

Primary Outcomes

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

Time frame: Baseline, Day 43

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

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.

Time frame: Time from randomization to the first Relapse during the maintenance phase (up to 2 years and 10 months)

Secondary Outcomes

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

Time frame: 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

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.

Time frame: Baseline, Day 43

Part 1: Change from Baseline in the MADRS-6 Total Score at 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).

Time frame: 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

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

Time frame: 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

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.

Time frame: 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 (10a) T-score at 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.

Time frame: Baseline, Day 43

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

Time frame: Baseline, Day 43

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

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.

Time frame: 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