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

NCT04533529 | Completed Phase 3 DMC FDA Drug

• 3 other identifiers: CR1088042020-000337-4042847922MDD3001
• Study Type: interventional
• Target: 588
• Locations: 11 countries
• Sites: 122

Brief 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.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (15)

• Double-blind (DB) Treatment Phase: 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.

  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

  Number of participants with AE including AE of special interest as a measure of safety and tolerability will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. AESI will comprise of cataplexy, sleep paralysis, complex, sleep-related behaviors/parasomnias, sleep terrors, bruxism, sleep sex, sleep related eating disorder, catathrenia, fall and motor vehicle accident.

  1 year

• OL Treatment Phase: Change From Baseline in Blood Pressure

  Change from baseline in blood pressure will be reported.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change From Baseline in Pulse Rate

  Change from baseline in pulse rate will be reported.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change From Baseline in Weight

  Change from baseline in weight as a part of physical examination will be reported.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change From Baseline in Body Mass Index (BMI)

  Change from baseline in BMI as a part of physical examination will be reported.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change From Baseline in Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS)

  Change from baseline in suicidality assessment using C-SSRS will be reported. C-SSRS is a clinician rated assessment of suicidal behavior and/or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses are listed. Worsening of suicidal ideation indicates an increase in severity of suicidal ideation from baseline. Suicidal behavior consists of 5 'yes/no' items: preparatory acts or behavior, aborted attempt, actual attempt, completed suicide.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Physician Withdrawal Checklist (PWC-20) Scores

  Withdrawal symptoms assessment using the PWC-20 will be reported. The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition.

  End of Treatment/Early withdrawal to end of the Follow-up visit (up to 14 days)

• OL Treatment Phase: Number of Participants with Laboratory Abnormalities

  Number of participants with laboratory abnormalities related to hematology, serum chemistry, coagulation, liver function tests and urinalysis will be reported.

  Up to 1 year

• OL Treatment Phase: Change From Baseline in QTc Interval

  Change from baseline in QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiogram (ECG).

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change from Baseline in Heart Rate (HR)

  Change from baseline in HR will be measured by ECG.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change from Baseline in QRS Interval

  Change from baseline in QRS interval will be measured by ECG.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change from Baseline in PR Interval

  Change from baseline in PR interval will be measured by ECG.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Change From Baseline in QT Interval

  Change from baseline in QT interval will be measured by ECG.

  Baseline (Day 43), up to 1 year

• OL Treatment Phase: Participant-reported Sexual Functioning Using Arizona Sexual Experiences Scale (ASEX) Score

  The ASEX is a patient-reported 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. The total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.

  Up to 1 year

Secondary Outcomes (10)

• 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

Study Arms (2)

Seltorexant

EXPERIMENTAL

Participants will receive seltorexant tablet orally once daily, from Day 1 to Day 42 in double blind (DB) treatment phase. Eligible participants who will enter the open label (OL) treatment phase will receive seltorexant tablet daily from OL baseline until the end of phase/ early withdrawal (EW) visit (Up to 1 Year).

Drug: Seltorexant

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo tablet orally once daily, from Day 1 to Day 42 in double blind (DB) treatment phase.

Drug: Placebo

Interventions

Seltorexant DRUG

Seltorexant tablet will be administered orally once daily.

Also known as: JNJ-42847922

Seltorexant

Placebo DRUG

Matching placebo tablet will be administered orally once daily.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (122)

Advanced Research Center Inc

Anaheim, California, 92805, United States

Location

Synexus

Cerritos, California, 90703, United States

Location

Irvine Clinical Research

Irvine, California, 92614, United States

Location

Omega Clinical Trials LLC

La Habra, California, 90631, United States

Location

Synergy East

Lemon Grove, California, 91945, United States

Location

Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, 90048, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

Pacific Research Partners

Oakland, California, 94607, United States

Location

North County Clinical Research

Oceanside, California, 92056, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Viking Pharmaceutical Trials Inc. dba Viking Clinical Research

Temecula, California, 92591, United States

Location

Connecticut Clinical Trials LLC

Cromwell, Connecticut, 06416, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Clinical NeuroScience Solutions Inc

Jacksonville, Florida, 32256, United States

Location

Pharmax Research Clinic Inc

Miami, Florida, 33126, United States

Location

Medical Research Center of Miami II Inc

Miami, Florida, 33134, United States

Location

Phoenix Medical Research, Inc.

Miami, Florida, 33165, United States

Location

Galiz Research

Miami Springs, Florida, 33166, United States

Location

Bravo Health Care Center

North Bay Village, Florida, 33141, United States

Location

APG Research LLC

Orlando, Florida, 32803, United States

Location

Combined Research Orlando

Orlando, Florida, 32803, United States

Location

Nova Psychiatry INC

Orlando, Florida, 32803, United States

Location

Revive Research Institute

Elgin, Illinois, 60123, United States

Location

Joliet Center for Clinical Research

Joliet, Illinois, 60435, United States

Location

Baber Research Group

Naperville, Illinois, 60563, United States

Location

American Medical Research, Inc.

Oak Brook, Illinois, 60523, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62701, United States

Location

Louisiana Clinical Research

Shreveport, Louisiana, 71101, United States

Location

Adams Clinical

Watertown, Massachusetts, 02472, United States

Location

Neurobehavioral Medicine Group

Bloomfield Hills, Michigan, 48302, United States

Location

Midwest Research Group - St. Charles Psychiatric Associates

Saint Charles, Missouri, 63301, United States

Location

Mid-America Clinical Research, LLC

St Louis, Missouri, 63109, United States

Location

PsychCare Consultants Research

St Louis, Missouri, 63128, United States

Location

Premier Psychiatric Research Institute, LLC

Lincoln, Nebraska, 68526, United States

Location

Altea Research Institute

Las Vegas, Nevada, 89102, United States

Location

Hassman Research Institute, LLC.

Berlin, New Jersey, 08009, United States

Location

Synexus Clinical Research US Inc

Jamaica, New York, 11432, United States

Location

Bioscience Research LLC

Mount Kisco, New York, 10549, United States

Location

Haidar Almhana Nieding

Avon Lake, Ohio, 44012, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

Lindner Center of Hope

Mason, Ohio, 45040, United States

Location

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, 73112, United States

Location

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18104, United States

Location

University of Pennsylvania - Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Relaro Medical Trials

Dallas, Texas, 75243, United States

Location

North Texas Clinical Trials

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Red Oak Psychiatry Associates

Houston, Texas, 77090, United States

Location

Alpine Research Organization

Clinton, Utah, 84015, United States

Location

Green Mountain Research Institute

Rutland, Vermont, 05701, United States

Location

CPN - Centro de Pesquisa em Neurociências Ltda

Belo Horizonte, 30150-270, Brazil

Location

CCB Centro Cardiologico de Brasilia Ltda - CCB Cardiologia

Brasília, 70200-730, Brazil

Location

Instituto de Neurologia de Curitiba

Curitiba, 81210-310, Brazil

Location

Universidade Federal do Ceara Hospital Universitario Walter Cantidio

Fortaleza, 60430-380, Brazil

Location

Instituto Mederi de Pesquisa e Saude

Passo Fundo, 99010-120, Brazil

Location

Ruschel Medicina e Pesquisa Clínica Ltda

Rio de Janeiro, 22270 060, Brazil

Location

SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo

São Paulo, 04037-003, Brazil

Location

Instituto Bairral de Psiquiatria

São Paulo, 13970-905, Brazil

Location

Mental Health Center Prof. Dr. Ivan Temkov

Burgas, 8001, Bulgaria

Location

Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET

Cherven Bryag, 5980, Bulgaria

Location

State Psychiatric Hospital Kardzhali

Kardzhali, 6600, Bulgaria

Location

Medical center Spectar - Plovdiv EOOD

Plovdiv, 4000, Bulgaria

Location

UMHAT 'Sv. Georgi' EAD

Plovdiv, 4000, Bulgaria

Location

MHC - Sofia, EOOD

Slivnitsa, 1202, Bulgaria

Location

Medical Center St. Naum

Sofia, 1113, Bulgaria

Location

DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD

Sofia, 1408, Bulgaria

Location

Medical Center Intermedica, OOD

Sofia, 1680, Bulgaria

Location

Medical center - VAS OOD

Targovishte, 7700, Bulgaria

Location

Mental Health Center - Vratsa EOOD

Vratsa, 3000, Bulgaria

Location

Centro de Investigaciones y Proyectos en Neurociencias CIPNA

Barranquilla, Colombia

Location

HOMO - ESE Hospital Mental de Antioquia

Bello, 051053, Colombia

Location

Centro de Investigaciones del Sistema Nervioso Grupo Cisne Ltda.

Bogotá, 111166, Colombia

Location

Fundacion Centro de Investigacion Clinica CIC

Medellín, Colombia

Location

Psynapsis Salud Mental S.A.

Pereira, Colombia

Location

BRAIN-SOULTHERAPY s.r.o.

Kladno, 27201, Czechia

Location

Neuroterapie KH S R O

Kutná Hora, 284 01, Czechia

Location

A Shine S R O

Pilsen, 31200, Czechia

Location

Clintrial s r o

Prague, 10000, Czechia

Location

Medical Services Prague S R O

Prague, 16000, Czechia

Location

Iecsi S.C.

Monterrey, 64310, Mexico

Location

CRI Centro Regiomontano de Investigacion SC

Nuevo León, 64060, Mexico

Location

Bind Investigaciones S.C.

San Luis Potosí City, 78213, Mexico

Location

Psychoneurological Dispensary of Frunzensky District

Saint Petersburg, 190013, Russia

Location

SPb SBIH 'City Psychoneurological Dispensary # 7 (With Inpatient Facilities)'

Saint Petersburg, 190020, Russia

Location

City Psychiatric Hospital of St. Nikolay Chudotvorets

Saint Petersburg, 190121, Russia

Location

Bekhterev Psychoneurological Research Institute

Saint Petersburg, 192019, Russia

Location

St-Petersburg Bekhterev Psychoneurological Research Institute

Saint Petersburg, 192019, Russia

Location

Psychoneurological dispensary 1

Saint Petersburg, 199106, Russia

Location

Stavropol Region Psychiatric Hospital #2

Stavropol, 357034, Russia

Location

Yaroslavl Region Clinical Psychiatric Hospital

Yaroslavl, 150003, Russia

Location

Farmovs Pty Ltd

Bloemfontein, 9301, South Africa

Location

Iatros International

Bloemfontein, 9324, South Africa

Location

Cape Town Clinical Research Centre

Cape Town, 7530, South Africa

Location

Flexivest 14 Research

Cape Town, 7530, South Africa

Location

DJW Research

Krugersdorp, 1739, South Africa

Location

Stanza Clinical Research Centre : Mamelodi

Mamelodi East, 0122, South Africa

Location

Synexus Watermeyer

Pretoria, South Africa

Location

Somerset West Clinical Research Unit

Strand, 7140, South Africa

Location

Institucion Hosp Hestia Palau

Barcelona, 08025, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp. Univ. de Basurto

Bilbao, 48013, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Centro Salud Mental La Corredoria

Oviedo, 33011, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Corporacio Sanitari Parc Tauli

Sabadell, 08208, Spain

Location

Centro de salud San Juan - IBSAL

Salamanca, 37005, Spain

Location

Hosp. Prov. de Zamora

Zamora, 49021, Spain

Location

Affecta Pskyiatrimottagning

Halmstad, SE-30248, Sweden

Location

PharmaSite Helsingborg

Helsingborg, 25220, Sweden

Location

ProbarE i Lund AB

Lund, 22222, Sweden

Location

PharmaSite

Malmo, 21152, Sweden

Location

Läkarmottagningen

Skövde, 54143, Sweden

Location

ProbarE i Solna

Stockholm, 111 37, Sweden

Location

Chang-Gung Memorial Hospital-Keelung

Keelung, 204, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10449, Taiwan

Location

Taipei Medical University

Taipei, 110, Taiwan

Location

Cheng Hsin General Hospital

Taipei, 112, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Memorial Hospital- Linkou

Taoyuan, 33305, Taiwan

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

seltorexant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 31, 2020
• Study Start: September 16, 2020
• Primary Completion: April 25, 2023
• Study Completion: April 30, 2024
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

US (51); CO (5); CZ (5); SE (6); TW (7); BU (11); BR (8); RU (8); ES (10); ZA (8); ME (3)