A Phase 3 interventional study of Seltorexant and Matching placebo to Seltorexant in Depressive Disorder, Major, sponsored by Janssen Research & Development, LLC. Completed at 175 sites in 15 countries. Open to participants aged 18 Years to 74 Years. Per ClinicalTrials.gov, last updated 2025-08-13.
Sponsored by Janssen Research & Development, LLC · Phase 3, Interventional, and Treatment
The purpose of this study is to assess the efficacy of seltorexant compared with quetiapine extended-release (XR) as adjunctive therapy to an antidepressant drug in treatment response 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).
Major depressive disorder (MDD) is a common, serious, recurrent disorder. Seltorexant (JNJ-42847922) is a potent and selective antagonist of the human orexin-2 receptor (OX2R) that is being developed for the adjunctive treatment of MDDIS. The hypothesis for this study is that seltorexant is superior to quetiapine XR in leading to a response after 26 weeks of treatment (greater than or equal to [>=] 50 percent [%] improvement on baseline Montgomery Asberg Depression Rating Scale [MADRS] total score), when administered as adjunctive treatment to an antidepressant in adult and elderly participants with MDDIS who have had an inadequate response to treatment with an SSRI/SNRI. The study will be conducted in 3 phases: a screening phase (up to 30 days), a double-blind (DB) treatment phase (26 weeks), and a post treatment follow-up phase (7 to 14 days after the end of DB treatment phase for all participants, and up to 196 days from baseline for participants who stop study treatment early). The total study duration for each participant will be approximately 32 weeks. Efficacy, safety, pharmacokinetics, and biomarkers will be assessed at specified time points during this study.
2,741 studies on the registry are indexed under Depressive Disorder, Major; 559 are open to participants now.
This study's enrollment of 757 is above the median of 80 across 2,283 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Janssen Research & Development, LLC is the lead sponsor of 912 studies on the registry; 76 are open to participants now.
Of its 278 completed or terminated interventional studies of FDA-regulated products, 131 (47%) have results posted.
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Exclusion Criteria:
Adult participants will receive seltorexant once daily from Day 1-7 and together with matching placebo from Day 8 till Day 182. Elderly participants will receive seltorexant once daily from Day 1-3 and together with matching placebo from Day 4 till Day 182.
Drug: Seltorexant · Drug: Matching placebo to Seltorexant
Adult participants will receive quetiapine XR once daily from Day 1-2, followed by an increase in dose from Day 3-7, and from Day 8-14 together with matching placebo. After Day 14, quetiapine XR twice daily from Day 14 till Day 182. Elderly participants will receive quetiapine XR once daily from Day 1-3 and twice from Day 4-7, followed by an increase in dose once daily from Day 8-14 together with matching placebo. After Day 14 till Day 182, quetiapine XR will be adjusted by investigator based on the participant's clinical response and tolerability.
Drug: Quetiapine XR · Drug: Matching placebo to Quetiapine XR
Participants will receive seltorexant over-encapsulated tablet orally.
Participants will receive placebo over-encapsulated tablet matching to seltorexant orally.
Participants will receive quetiapine XR capsule orally.
Participants will receive placebo capsule matching to quetiapine XR orally.
Percentage of Participants with Response (>=50 Percent improvement in MADRS total score from baseline) at Week 26
Responders are defined as percentage of participants with greater than or equal to (\>=) 50 percent (%) improvement in the montgomery-asberg depression rating scale (MADRS) total score from baseline. MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item 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: Week 26
Change from baseline in Weight up to Week 26
Change from baseline in weight will be reported.
Time frame: Baseline to Week 26
Time to Study Drug Discontinuation for Potentially Treatment Related Reasons
Time to discontinuation of study drug for potentially treatment related reasons will be reported. Potentially treatment related reasons are defined as all study drug discontinuations excluding the potentially non-treatment related discontinuations (eg, loss of insurance for antidepressant therapy, movement/travel out of the area, change of work-schedule being unable to accommodate visit schedule, family circumstances).
Time frame: Up to Week 26
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item 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 to Week 26
Change from Baseline in MADRS-6 Total Score
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).
Time frame: Baseline to Week 26
Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score
The MADRS is a 10-item clinician-rated instrument for evaluating severity of symptoms of depression. Each item is rated on a scale from 0 to 6, with higher scores indicating greater symptom severity. 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 to Week 26
Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score
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 to Week 26
Percentage of Participants with Remission (MADRS Total Score less than or equal to (<=) 12) at Week 26
Percentage of participants with remission (MADRS total Score \<=12) will be reported.
Time frame: Week 26
Percentage of Participants with a >=50 Percent Improvement in MADRS Total Score and MADRS <=18 at Week 26
Percentage of participants with a \>=50 percent improvement in MADRS total score and MADRS \<=18 at Week 26.
Time frame: Week 26
Percentage of Participants with Weight Increase >=7 Percent from Baseline at Week 26
Percentage of participants with weight increase \>=7 percent from baseline will be reported.
Time frame: Week 26
Showing the first 100 of 175 sites across 15 countries.
Plan to share: Yes — The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical- trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu
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