A Multicenter, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy and an Open-labeled Long-term Safety Extension Treatment With Seltorexant

Plain English Summary

A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant and Long-term Safety Extension Treatment With Seltorexant is a Phase 3 clinical trial sponsored by Janssen Research & Development, LLC studying Depressive Disorder, Major. Tests seltorexant as an adjunct to antidepressants for major depressive disorder with insomnia symptoms. For adults and elderly patients who have not responded adequately to antidepressants. Participation involves taking seltorexant or placebo tablets daily and attending regular check-ups. Alternative treatments include other antidepressants or cognitive behavioral therapy. The trial aims to enroll 588 participants.

Official Summary

The purpose of this study is to assess the efficacy of seltorexant compared with placebo as 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 an selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in double-blind treatment phase and to assess the long-term safety and tolerability of seltorexant as adjunctive therapy to an antidepressant in participants with major depressive disorder (MDD) in open-label treatment phase.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if diagnosed with major depressive disorder, aged 18-85, and have insomnia symptoms. Not eligible if have severe kidney issues, recent suicidal thoughts, or other serious health conditions. Must be stable on current antidepressant treatment for at least 6 weeks. Must not have a history of substance use disorder or psychotic disorders. This trial is studying Depressive Disorder, Major, so participants generally need a confirmed diagnosis.

What They're Measuring

Primary outcomes measure changes in depression severity and sleep quality, providing insights into the treatment's effectiveness. The specific primary outcome measures are: Double-blind (DB) Treatment Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Baseline, Day 43); Open-Label (OL) Treatment Phase: Number of Participants with Adverse Events (AEs) including AEs of Special Interest (AESI) as a Measure of Safety and Tolerability (1 year); OL Treatment Phase: Change From Baseline in Blood Pressure (Baseline (Day 43), up to 1 year); OL Treatment Phase: Change From Baseline in Pulse Rate (Baseline (Day 43), up to 1 year); OL Treatment Phase: Change From Baseline in Weight (Baseline (Day 43), up to 1 year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial fills a gap by evaluating a new treatment for major depressive disorder with insomnia, a common but challenging condition. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Depressive Disorder, Major, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high probability of approval, making this a promising investment opportunity. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 588 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you meet the criteria for major depressive disorder with insomnia and have not responded well to antidepressants. Participation involves daily medication and regular check-ups at clinical research facilities. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 588 participants

Interventions

• DRUG: Seltorexant — Seltorexant tablet will be administered orally once daily.
• DRUG: Placebo — Matching placebo tablet will be administered orally once daily.

Primary Outcomes

• Double-blind (DB) Treatment Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Baseline, Day 43)
• Open-Label (OL) Treatment Phase: Number of Participants with Adverse Events (AEs) including AEs of Special Interest (AESI) as a Measure of Safety and Tolerability (1 year)
• OL Treatment Phase: Change From Baseline in Blood Pressure (Baseline (Day 43), up to 1 year)
• OL Treatment Phase: Change From Baseline in Pulse Rate (Baseline (Day 43), up to 1 year)
• OL Treatment Phase: Change From Baseline in Weight (Baseline (Day 43), up to 1 year)

Secondary Outcomes

• DB Treatment Phase: Change From Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score (Baseline and Day 43)
• DB Treatment Phase: Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a T-score (Baseline and Day 43)
• DB Treatment Phase: Change From Baseline in the MADRS-6 Total Score (Baseline and Day 43)
• DB Treatment Phase: Percentage of Participants with Response on Depressive Symptoms Scale Based on Montgomery-Asberg Depression Rating Scale (MADRS) (Day 43)
• DB Treatment Phase: Change From Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score (Baseline and Day 43)

Full Eligibility Criteria

Inclusion Criteria:

* Meet Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) diagnostic criteria for major depressive disorder (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. The length of the current depressive episode must be less than or equal to (\<=) 24 months prior to randomization
* 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. The current antidepressant cannot be the first antidepressant treatment for the first lifetime episode of depression. An inadequate response is defined as less than (\<) 50 percent (%) reduction but with some improvement (that is, improvement greater than \[\>\] 0%) in depressive symptom severity with residual symptoms beyond insomnia present, and overall good tolerability, as assessed by the Massachusetts General Hospital-Antidepressant Treatment Response Questionnaire (MGH-ATRQ)
* Is receiving and tolerating well any one of the following selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (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, and for no greater than 18 months in the current episode
* Body mass index (BMI) between 18 and 40 kilograms per meter square (kg/m\^2), inclusive (BMI = weight/height\^2)
* Participant must be medically stable on the basis of the following performed at screening: physical examination (including a brief neurological examination), vital signs (including blood pressure), and 12-lead electrocardiogram (ECG) performed at screening and baseline

Exclusion Criteria:

* Has a recent (last 3 months) history of, or current signs and symptoms of, a) severe renal insufficiency (creatinine clearance \[CrCl\] \<30 milliliter per minute \[mL/min\]); b) clinically significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders; c) uncontrolled Type 1 or Type 2 diabetes mellitus
* Has a current or recent history of homicidal ideation or serious suicidal ideation within the past 3 months, corresponding to a positive response on item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) for ideation on the Columbia Suicide Severity Rating Scale (C-SSRS), or a history of suicidal behavior within the past 6 months, as validated by the C-SSRS at screening or Day 1. Participants with prior suicidal behavior in the past year, or prior serious suicidal ideation/plan within the past 6 months, should be carefully screened. For current suicidal ideation, only participants with non serious items (1-3 of the suicidal ideation section of the C-SSRS) may be included at the discretion of the investigator
* Has a history of treatment-resistant MDD, defined as a lack of response to 2 or more adequate antidepressant treatments in the current episode, as indicated by no or minimal (\<25% improvement in symptoms) when treated with an antidepressant of adequate dose (per MGH-ATRQ) and duration (at least 6 weeks)
* Has history or current diagnosis of a psychotic disorder, bipolar disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, or somatoform disorders
* Has any significant primary sleep disorder, including but not limited to obstructive sleep apnea, restless leg syndrome, or parasomnias. Participants with insomnia disorder are allowed
* Has a history of moderate to severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening

Trial Locations

• Advanced Research Center Inc, Anaheim, California, United States
• Synexus, Cerritos, California, United States
• Irvine Clinical Research, Irvine, California, United States
• Omega Clinical Trials LLC, La Habra, California, United States
• Synergy East, Lemon Grove, California, United States
• Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, United States
• Catalina Research Institute, Montclair, California, United States
• Pacific Research Partners, Oakland, California, United States
• North County Clinical Research, Oceanside, California, United States
• Syrentis Clinical Research, Santa Ana, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Major Depressive Disorder, Insomnia, Sleep Disorders, Anxiety Disorders, Bipolar Disorder

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