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

Plain English Summary

Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms is a Phase 3 clinical trial sponsored by Janssen Research & Development, LLC studying Depressive Disorder, Major. Tests how well seltorexant works as an add-on treatment to antidepressants for major depressive disorder with insomnia symptoms. For adults and elderly participants with major depressive disorder and insomnia who have not responded well to previous antidepressants. Participation involves taking seltorexant or placebo tablets and attending regular clinic visits. Alternative treatments include other antidepressants and psychotherapy. The trial aims to enroll 752 participants.

Official 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).

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible participants must have a major depressive episode and have tried at least one but no more than two antidepressants. Participants must be taking a stable dose of an SSRI or SNRI for at least 6 weeks. Age range is 18-85 years. Good overall health and no severe medical conditions. This trial is studying Depressive Disorder, Major, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the improvement in depressive symptoms and the maintenance of that effect over time, providing hope for better management of these symptoms. The specific primary outcome measures are: Part 1: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 43 (Baseline, Day 43); Part 2: Time from Randomization to the First Relapse in Participants Who Achieve a Stable Response (Time from randomization to the first Relapse during the maintenance phase (up to 2 years and 10 months)). 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 aims to fill a treatment gap for patients with major depressive disorder and insomnia who have not responded to previous treatments. 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 approval probability, with a significant unmet need in this therapeutic area. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 752 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have had an inadequate response to antidepressants and if you have insomnia symptoms. Participation involves regular clinic visits and taking study medication. This trial is currently recruiting participants. 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: 752 participants

Interventions

• DRUG: Seltorexant — Seltorexant will be administered orally.
• DRUG: Placebo — Matching Placebo tablets will be administered orally.
• DRUG: Selective Serotonin Reuptake Inhibitor (SSRI)/Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) — SSRI/SNRI will be administered orally.

Primary Outcomes

• Part 1: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 43 (Baseline, Day 43)
• Part 2: Time from Randomization to the First Relapse in Participants Who Achieve a Stable Response (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 (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 (Baseline, Day 43)
• Part 1: Change from Baseline in the MADRS-6 Total Score at Day 43 (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 (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 (Baseline, Day 43)

Full Eligibility Criteria

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

Trial Locations

• 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
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

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

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