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

NCT ID: NCT04533529

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 588 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-16
• Study Completion Date: 2024-04-30

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.

Detailed Description

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 adjunctive treatment of major depressive disorder with insomnia symptoms (MDDIS). The hypothesis for this study is that adjunctive treatment with seltorexant is superior to placebo in treating depressive symptoms, as measured by change in Montgomery Asberg Depression Rating Scale (MADRS) total score from baseline to Day 43 in adult and elderly participants with MDDIS who have had an inadequate response to treatment with a SSRI/SNRI. The study will be conducted in 4 phases: a screening phase (up to 30 days), a double-blind (DB) treatment phase (43 days), open label (OL) treatment phase (1-year), and a post treatment follow-up phase (7 to 14 days after end of treatment). The total study duration for each participant will be up to 64 weeks. Efficacy, safety, pharmacokinetics, and biomarkers will be assessed at specified time points during this study.

Conditions

Depressive Disorder, Major

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Seltorexant

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).

Group Type: EXPERIMENTAL

Seltorexant

Intervention Type: DRUG

Seltorexant tablet will be administered orally once daily.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablet will be administered orally once daily.

Interventions

Seltorexant

Seltorexant tablet will be administered orally once daily.

Intervention Type: DRUG

Placebo

Matching placebo tablet will be administered orally once daily.

Intervention Type: DRUG

Other Intervention Names

JNJ-42847922

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

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

Viking Pharmaceutical Trials Inc. dba Viking Clinical Research

Temecula, California, United States

Connecticut Clinical Trials LLC

Cromwell, Connecticut, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Sarkis Clinical Trials

Gainesville, Florida, United States

Clinical NeuroScience Solutions Inc

Jacksonville, Florida, United States

Pharmax Research Clinic Inc

Miami, Florida, United States

Medical Research Center of Miami II Inc

Miami, Florida, United States

Phoenix Medical Research, Inc.

Miami, Florida, United States

Galiz Research

Miami Springs, Florida, United States

Bravo Health Care Center

North Bay Village, Florida, United States

APG Research LLC

Orlando, Florida, United States

Combined Research Orlando

Orlando, Florida, United States

Nova Psychiatry INC

Orlando, Florida, United States

Revive Research Institute

Elgin, Illinois, United States

Joliet Center for Clinical Research

Joliet, Illinois, United States

Baber Research Group

Naperville, Illinois, United States

American Medical Research, Inc.

Oak Brook, Illinois, United States

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Louisiana Clinical Research

Shreveport, Louisiana, United States

Adams Clinical

Watertown, Massachusetts, United States

Neurobehavioral Medicine Group

Bloomfield Hills, Michigan, United States

Midwest Research Group - St. Charles Psychiatric Associates

Saint Charles, Missouri, United States

Mid-America Clinical Research, LLC

St Louis, Missouri, United States

PsychCare Consultants Research

St Louis, Missouri, United States

Premier Psychiatric Research Institute, LLC

Lincoln, Nebraska, United States

Altea Research Institute

Las Vegas, Nevada, United States

Hassman Research Institute, LLC.

Berlin, New Jersey, United States

Synexus Clinical Research US Inc

Jamaica, New York, United States

Bioscience Research LLC

Mount Kisco, New York, United States

Haidar Almhana Nieding

Avon Lake, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

Lindner Center of Hope

Mason, Ohio, United States

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, United States

Lehigh Center for Clinical Research

Allentown, Pennsylvania, United States

University of Pennsylvania - Perelman School of Medicine

Philadelphia, Pennsylvania, United States

Relaro Medical Trials

Dallas, Texas, United States

North Texas Clinical Trials

Fort Worth, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Red Oak Psychiatry Associates

Houston, Texas, United States

Alpine Research Organization

Clinton, Utah, United States

Green Mountain Research Institute

Rutland, Vermont, United States

CPN - Centro de Pesquisa em Neurociências Ltda

Belo Horizonte, , Brazil

CCB Centro Cardiologico de Brasilia Ltda - CCB Cardiologia

Brasília, , Brazil

Instituto de Neurologia de Curitiba

Curitiba, , Brazil

Universidade Federal do Ceara Hospital Universitario Walter Cantidio

Fortaleza, , Brazil

Instituto Mederi de Pesquisa e Saude

Passo Fundo, , Brazil

Ruschel Medicina e Pesquisa Clínica Ltda

Rio de Janeiro, , Brazil

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

São Paulo, , Brazil

Instituto Bairral de Psiquiatria

São Paulo, , Brazil

Mental Health Center Prof. Dr. Ivan Temkov

Burgas, , Bulgaria

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

Cherven Bryag, , Bulgaria

State Psychiatric Hospital Kardzhali

Kardzhali, , Bulgaria

Medical center Spectar - Plovdiv EOOD

Plovdiv, , Bulgaria

UMHAT 'Sv. Georgi' EAD

Plovdiv, , Bulgaria

MHC - Sofia, EOOD

Slivnitsa, , Bulgaria

Medical Center St. Naum

Sofia, , Bulgaria

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

Sofia, , Bulgaria

Medical Center Intermedica, OOD

Sofia, , Bulgaria

Medical center - VAS OOD

Targovishte, , Bulgaria

Mental Health Center - Vratsa EOOD

Vratsa, , Bulgaria

Centro de Investigaciones y Proyectos en Neurociencias CIPNA

Barranquilla, , Colombia

HOMO - ESE Hospital Mental de Antioquia

Bello, , Colombia

Centro de Investigaciones del Sistema Nervioso Grupo Cisne Ltda.

Bogotá, , Colombia

Fundacion Centro de Investigacion Clinica CIC

Medellín, , Colombia

Psynapsis Salud Mental S.A.

Pereira, , Colombia

BRAIN-SOULTHERAPY s.r.o.

Kladno, , Czechia

Neuroterapie KH S R O

Kutná Hora, , Czechia

A Shine S R O

Pilsen, , Czechia

Clintrial s r o

Prague, , Czechia

Medical Services Prague S R O

Prague, , Czechia

Iecsi S.C.

Monterrey, , Mexico

CRI Centro Regiomontano de Investigacion SC

Nuevo León, , Mexico

Bind Investigaciones S.C.

San Luis Potosí City, , Mexico

Psychoneurological Dispensary of Frunzensky District

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

City Psychiatric Hospital of St. Nikolay Chudotvorets

Saint Petersburg, , Russia

Bekhterev Psychoneurological Research Institute

Saint Petersburg, , Russia

St-Petersburg Bekhterev Psychoneurological Research Institute

Saint Petersburg, , Russia

Psychoneurological dispensary 1

Saint Petersburg, , Russia

Stavropol Region Psychiatric Hospital #2

Stavropol, , Russia

Yaroslavl Region Clinical Psychiatric Hospital

Yaroslavl, , Russia

Farmovs Pty Ltd

Bloemfontein, , South Africa

Iatros International

Bloemfontein, , South Africa

Cape Town Clinical Research Centre

Cape Town, , South Africa

Flexivest 14 Research

Cape Town, , South Africa

DJW Research

Krugersdorp, , South Africa

Stanza Clinical Research Centre : Mamelodi

Mamelodi East, , South Africa

Synexus Watermeyer

Pretoria, , South Africa

Somerset West Clinical Research Unit

Strand, , South Africa

Institucion Hosp Hestia Palau

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Univ. de Basurto

Bilbao, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp. Univ. La Paz

Madrid, , Spain

Centro Salud Mental La Corredoria

Oviedo, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Centro de salud San Juan - IBSAL

Salamanca, , Spain

Hosp. Prov. de Zamora

Zamora, , Spain

Affecta Pskyiatrimottagning

Halmstad, , Sweden

PharmaSite Helsingborg

Helsingborg, , Sweden

ProbarE i Lund AB

Lund, , Sweden

PharmaSite

Malmo, , Sweden

Läkarmottagningen

Skövde, , Sweden

ProbarE i Solna

Stockholm, , Sweden

Chang-Gung Memorial Hospital-Keelung

Keelung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

Taipei Medical University

Taipei, , Taiwan

Cheng Hsin General Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital- Linkou

Taoyuan, , Taiwan

Countries

United States; Brazil; Bulgaria; Colombia; Czechia; Mexico; Russia; South Africa; Spain; Sweden; Taiwan

Other Identifiers

2020-000337-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

42847922MDD3001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108804

Identifier Type: -

Identifier Source: org_study_id