Double-Blind, Randomized, Parallel-Group Study With Quetiapine Extended Release as Comparator 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

Plain English Summary

A Study of Seltorexant Compared to Quetiapine XR as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy is a Phase 3 clinical trial sponsored by Janssen Research & Development, LLC studying Depressive Disorder, Major. Tests if seltorexant is as effective as quetiapine in treating depression with insomnia in adults and elderly who haven't responded well to antidepressants. For adults and elderly with major depressive disorder and insomnia who have tried 1-2 antidepressants without full improvement. Participation involves taking daily medication and regular check-ups. Side effects are monitored closely. Alternative treatments include other antidepressants or sleep aids prescribed by a doctor. The trial aims to enroll 757 participants.

Official Summary

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).

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if over 18, diagnosed with major depressive disorder, tried 1-2 antidepressants, and have insomnia symptoms. Not eligible if have severe kidney problems, history of severe mental illness, or substance abuse in the last 6 months. Age range: 18-80 years. Good overall health, no major medical conditions. This trial is studying Depressive Disorder, Major, so participants generally need a confirmed diagnosis.

What They're Measuring

Measures improvement in depression symptoms and quality of life, helping patients manage their condition better. The specific primary outcome measures are: Percentage of Participants with Response (>=50 Percent improvement in MADRS total score from baseline) at Week 26 (Week 26). 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 depression with insomnia, offering an alternative to existing medications. 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

Significant market need, competitive landscape with limited options, high approval probability given positive results. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 757 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 have insomnia. Daily medication and regular check-ups are required. 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: 757 participants

Interventions

• DRUG: Seltorexant — Participants will receive seltorexant over-encapsulated tablet orally.
• DRUG: Matching placebo to Seltorexant — Participants will receive placebo over-encapsulated tablet matching to seltorexant orally.
• DRUG: Quetiapine XR — Participants will receive quetiapine XR capsule orally.
• DRUG: Matching placebo to Quetiapine XR — Participants will receive placebo capsule matching to quetiapine XR orally.

Primary Outcomes

• Percentage of Participants with Response (>=50 Percent improvement in MADRS total score from baseline) at Week 26 (Week 26)

Secondary Outcomes

• Change from baseline in Weight up to Week 26 (Baseline to Week 26)
• Time to Study Drug Discontinuation for Potentially Treatment Related Reasons (Up to Week 26)
• Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Baseline to Week 26)
• Change from Baseline in MADRS-6 Total Score (Baseline to Week 26)
• Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score (Baseline to Week 26)

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
* 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 present other than insomnia, 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 or above therapeutic dose level) for at least 6 weeks, and for no greater than 18 months in the current episode
* Have a hamilton depression rating scale (HDRS)-17 total score greater than or equal to (\>=) 20 at the first screening interview, must not demonstrate a clinically significant improvement (that is, an improvement of \> 20% on their HDRS-17 total score) from the first to the second independent HDRS-17 rating, and must have a HDRS-17 total score \>18 at the second screening interview
* Have a patient version insomnia severity index (ISI) total score \>= 15 as well as a clinician version of the ISI total score \>= 15 at the second screening visit
* Body mass index (BMI) between 18 and 40 kilogram per meter square (kg/m\^2), inclusive (BMI=weight/height\^2)
* Participant must be medically stable on the basis of the following: physical 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, severe renal insufficiency (creatinine clearance \[CrCl\] less than \[\<\] 30 milliliter per minute \[mL/min\]); clinically significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders. uncontrolled Type 1 or Type 2 diabetes mellitus
* 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, somatoform disorders
* Has a history of moderate to severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening
* 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

Trial Locations

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• SW Biomedical Research LLC, Tucson, Arizona, United States
• Proscience Research Group, Culver City, California, United States
• Pharmacology Research Institute, Encino, California, United States
• Collaborative NeuroScience Network, Garden Grove, California, United States
• Collaborative NeuroScience Network, Long Beach, California, United States
• Pharmacology Research Institute, Los Alamitos, California, United States
• CalNeuro Research, Los Angeles, California, United States
• Pharmacology Research Institute, Newport Beach, California, United States
• NRC Research Institute, Orange, 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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