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

NCT ID: NCT04513912

Last Updated: 2025-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 757 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2023-10-03

Brief 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).

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 the adjunctive treatment of MDDIS. The hypothesis for this study is that seltorexant is superior to quetiapine XR in leading to a response after 26 weeks of treatment (greater than or equal to [>=] 50 percent [%] improvement on baseline Montgomery Asberg Depression Rating Scale [MADRS] total score), when administered as adjunctive treatment to an antidepressant in adult and elderly participants with MDDIS who have had an inadequate response to treatment with an SSRI/SNRI. The study will be conducted in 3 phases: a screening phase (up to 30 days), a double-blind (DB) treatment phase (26 weeks), and a post treatment follow-up phase (7 to 14 days after the end of DB treatment phase for all participants, and up to 196 days from baseline for participants who stop study treatment early). The total study duration for each participant will be approximately 32 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

Adult participants will receive seltorexant once daily from Day 1-7 and together with matching placebo from Day 8 till Day 182. Elderly participants will receive seltorexant once daily from Day 1-3 and together with matching placebo from Day 4 till Day 182.

Group Type: EXPERIMENTAL

Seltorexant

Intervention Type: DRUG

Participants will receive seltorexant over-encapsulated tablet orally.

Matching placebo to Seltorexant

Intervention Type: DRUG

Participants will receive placebo over-encapsulated tablet matching to seltorexant orally.

Quetiapine Extended-Release (XR)

Adult participants will receive quetiapine XR once daily from Day 1-2, followed by an increase in dose from Day 3-7, and from Day 8-14 together with matching placebo. After Day 14, quetiapine XR twice daily from Day 14 till Day 182. Elderly participants will receive quetiapine XR once daily from Day 1-3 and twice from Day 4-7, followed by an increase in dose once daily from Day 8-14 together with matching placebo. After Day 14 till Day 182, quetiapine XR will be adjusted by investigator based on the participant's clinical response and tolerability.

Group Type: ACTIVE_COMPARATOR

Quetiapine XR

Intervention Type: DRUG

Participants will receive quetiapine XR capsule orally.

Matching placebo to Quetiapine XR

Intervention Type: DRUG

Participants will receive placebo capsule matching to quetiapine XR orally.

Interventions

Seltorexant

Participants will receive seltorexant over-encapsulated tablet orally.

Intervention Type: DRUG

Matching placebo to Seltorexant

Participants will receive placebo over-encapsulated tablet matching to seltorexant orally.

Intervention Type: DRUG

Quetiapine XR

Participants will receive quetiapine XR capsule orally.

Intervention Type: DRUG

Matching placebo to Quetiapine XR

Participants will receive placebo capsule matching to quetiapine XR orally.

Intervention Type: DRUG

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

• 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

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

Pacific Neuropsychiatric Specialists

Orange, California, United States

CNRI-Los Angeles, LLC

Pico Rivera, California, United States

Prospective Research Innovations Inc

Rancho Cucamonga, California, United States

Anderson Clinical Research

Redlands, California, United States

University of California at San Diego

San Diego, California, United States

National Research Institute

Santa Ana, California, United States

CI Trials

Santa Ana, California, United States

CMB Clinical Trials

Santee, California, United States

Schuster Medical Research Institute

Sherman Oaks, California, United States

Pacific Clinical Research Medical Group

Upland, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Moonshine Research Center, Inc

Doral, Florida, United States

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, United States

Indago Research & Health Center Inc

Hialeah, Florida, United States

New Life Medical Research Center, Inc.

Hialeah, Florida, United States

Amedica Research Institute Inc

Hialeah, Florida, United States

Meridien Research

Lakeland, Florida, United States

Premier Clinical Research

Miami, Florida, United States

Global Medical Institutes

Miami, Florida, United States

Miami Jewish Health System

Miami, Florida, United States

Clinical Neuroscience Solutions

Orlando, Florida, United States

Synexus Research Orlando

Orlando, Florida, United States

University of South Florida

Tampa, Florida, United States

Compass Research LLC-Bioclinica Research

The Villages, Florida, United States

Synexus Clinical Research US Inc

Atlanta, Georgia, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

iResearch Atlanta LLC

Decatur, Georgia, United States

Psych Atlanta, P.C.

Marietta, Georgia, United States

Chicago Research Center

Chicago, Illinois, United States

Capstone Clinical Research

Libertyville, Illinois, United States

Alexian Brothers Health System

Lisle, Illinois, United States

Baber Research Group

Naperville, Illinois, United States

Lemah Creek Clinical Research

Oakbrook Terrace, Illinois, United States

Ascension via Christi Research

Wichita, Kansas, United States

Riverstar Research

New Orleans, Louisiana, United States

Pharmasite Research, Inc.

Baltimore, Maryland, United States

BTC of New Bedford

New Bedford, Massachusetts, United States

Boston Clinical Trials & Medical Research

Roslindale, Massachusetts, United States

Psychiatric Care and Research Center (PCRC)

O'Fallon, Missouri, United States

Bio Behavioral Health

Toms River, New Jersey, United States

SPRI Clinical Trials, LLC

Brooklyn, New York, United States

Fieve Clinical Research Inc

New York, New York, United States

The Medical Research Network, LLC

New York, New York, United States

Finger Lakes Clinical Research

Rochester, New York, United States

Richmond Behavioral Associates

Staten Island, New York, United States

Velocity Clinical Research, Inc.

Durham, North Carolina, United States

University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, United States

Midwest Clinical Research Center

Dayton, Ohio, United States

Neuro Behavioral Clinical Research

North Canton, Ohio, United States

Sooner Clinical Research

Oklahoma City, Oklahoma, United States

Paradigm Research Professionals, LLC

Oklahoma City, Oklahoma, United States

Suburban Research Associates

Pine Hill, Pennsylvania, United States

Global Medical Institutes

Scranton, Pennsylvania, United States

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, United States

West Houston Clinical Research Service

Bellaire, Texas, United States

North Texas Clinical Trials

Fort Worth, Texas, United States

Hawkins Psychiatry, PC

Mansfield, Texas, United States

Family Psychiatry of The Woodlands

The Woodlands, Texas, United States

Grayline Research Center

Wichita Falls, Texas, United States

Alpine Research Organization

Clinton, Utah, United States

Cedar Clinical Research

Draper, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

Core Clinical Research

Everett, Washington, United States

Cary J. Kohlenberg, MD, SC, dba, IPC Research.

Waukesha, Wisconsin, United States

CENydET - Centro Neurobiologico y de Stress Traumatico

Buenos Aires, , Argentina

Hospital Italiano

Buenos Aires, , Argentina

FunDaMos

Buenos Aires, , Argentina

Hospital Fleni

Ciudad Autonoma Buenos Aires, , Argentina

Fundacion Lennox

Córdoba, , Argentina

Instituto Privado Kremer

Córdoba, , Argentina

Centro Medico Luquez

Córdoba, , Argentina

CENPIA

La Plata, , Argentina

Clinica Privada de Salud Mental Santa Teresa de Ávila

La Plata, , Argentina

CENAIN

Mendoza, , Argentina

Clinica Mayo de UMCB

San Miguel de Tucumán, , Argentina

AZ Sint-Lucas

Bruges, , Belgium

AZ Nikolaas

Sint-Niklaas, , Belgium

Medical Center Medconsult-Pleven

Pleven, , Bulgaria

MC 'Hipokrat - N', EOOD

Plovdiv, , Bulgaria

Mental Health Center - Rousse

Rousse, , Bulgaria

Medical Center St. Naum

Sofia, , Bulgaria

Medical Center Intermedica, OOD

Sofia, , Bulgaria

MC 'Synexus Sofia' EOOD

Sofia, , Bulgaria

MC 'Synexus Sofia' EOOD

Stara Zagora, , Bulgaria

UMHAT Prof. Dr. St. Kirkovich AD

Stara Zagora, , Bulgaria

State Psychiatric Hospital - Tzarev Brod

Tzarev Brod, , Bulgaria

Diagnostic Consulting Center Mladost - M Varna

Varna, , Bulgaria

Mental Health Center - Veliko Tarnovo EOOD

Veliko Tarnovo, , Bulgaria

A.K. Munshi Medical Inc.

Sydney, Nova Scotia, Canada

Canadian Phase Onward

Toronto, Ontario, Canada

Clinique Force Medic (GCP Trials)

Montreal, Quebec, Canada

Psychiatricka ambulance Saint Anne s.r.o.

Brno, , Czechia

NeuropsychiatrieHK, s.r.o.

Hradec Králové, , Czechia

A Shine S R O

Pilsen, , Czechia

Clintrial s r o

Prague, , Czechia

AD71 s.r.o.

Prague, , Czechia

NeuropsychiatrieHK, s.r.o.

Prague, , Czechia

Institut Neuropsychiatricke pece

Prague, , Czechia

The Mental Hospital of Jelgava Ģintermuiža - Psychiatry

Jelgava, , Latvia

L. Keruze Practice in Psychiatry

Liepāja, , Latvia

Hospital of Rezekne

Outpatient Centre of Psychiatry, , Latvia

Riga Centre of Psychiatry and Narcology

Riga, , Latvia

Kaunas Silainiu Outpatient Clinic, Public Institution

Kaunas, , Lithuania

Republic Kaunas Hospital

Kaunas, , Lithuania

Romuvos Klinika, JSC

Kaunas, , Lithuania

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

Medical Center Puriena JSC

Šilutė, , Lithuania

Zirmunai Mental Health Center, Public Institution

Vilnius, , Lithuania

Antakalnis Psychiatric Consultation Centre, Public Institution

Vilnius, , Lithuania

Vilnius Mental Health Center

Vilnius, , Lithuania

Hospital Raja Permaisuri Bainun

Ipoh, , Malaysia

Hospital Permai

Johor Bahru, , Malaysia

Hospital Pulau Pinang

Pulau Pinang, , Malaysia

Hospital Tuanku Jaafar

Seremban, , Malaysia

Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski

Bełchatów, , Poland

Wlokiennicza MED Specjalistyczna Praktyka Lekarska dr n.med. Tomasz Markowski

Bialystok, , Poland

Przychodnia Srodmiescie SP. z o.o.

Bydgoszcz, , Poland

Centrum Badan Klinicznych PI House sp z o o

Gdansk, , Poland

Specjalistyczna Indywidualna Praktyka Lekarska

Lodz, , Poland

CCBR - Lodz - PL

Lodz, , Poland

Specjalistyczna Praktyka Lekarska Marek Domanski

Lublin, , Poland

Synexus Polska Sp. z.o.o. Oddzial w Poznaniu

Poznan, , Poland

Specjalistyczny Osrodek Medycyny Wieku Dojrzalego Sp z o.o.

Warsaw, , Poland

Instytut Psychiatrii I Neurologii

Warsaw, , Poland

Engels psychiatric hospital

Engel's, , Russia

Kemerovo Regional Clinical Psychiatric Hospital

Kemerovo, , Russia

GUZ Lipetsk Regional psychoneurological Hospital #1

Lipetsk Region, , Russia

JSC Scientific Centre of Personalized Medicine

Moscow, , Russia

FSI Moscow SRI of Psychiatry of Minzdravsocrazvitia

Moscow, , Russia

Moscow Scientific Research Institute of Psychiatry

Moscow, , Russia

Clinical Psychiatry Hospital n.a. N.N. Solodovnikov

Omsk, , Russia

St-Petersburg Bekhterev Psychoneurological Research Institute

Saint Petersburg, , Russia

Klinika StoLet Ltd

Tomsk, , Russia

Sverdlov Regional Psychiatric Clinical Hospital

Yekaterinburg, , Russia

General Hospital Acibadem Bel Medic

Belgrade, , Serbia

General Hospital Euromedik

Belgrade, , Serbia

Institute of Mental Health Serbia

Belgrade, , Serbia

University Clinical Center of Serbia

Belgrade, , Serbia

University Clinical Hospital Center Dr Dragisa Misovic- Dedi

Belgrade, , Serbia

Special Neuropsychiatric Hospital Kovin

Kovin, , Serbia

University Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical Center Nis

Niš, , Serbia

Specialized Hospital for Neuropsychiatric Diseases Sveti Vracevi

Novi Kneževac, , Serbia

Psychomed-Svatosavsky, s.r.o.

Banská Bystrica, , Slovakia

Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach

Bojnice, , Slovakia

Epamed sro

Košice, , Slovakia

Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu

Liptovský Mikuláš, , Slovakia

Psychiatricka Ambulancia Psycholine S.R.O.

Rimavská Sobota, , Slovakia

FN Trencin

Trenčín, , Slovakia

Pro mente sana s.r.o.

Trenčín, , Slovakia

Fakultna nemocnica s poliklinikou v Ziline

Žilina, , Slovakia

MNCE of Kyiv RC Regional Psychiatric and Narcological Medical Association

Hlevakha, , Ukraine

Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'

Kharkiv, , Ukraine

Kyiv Territorial Medical Incorporation 'Psychiatry'

Kyiv, , Ukraine

Railway Clinical Hospital #1 of Kiev Railway station of DTGO 'South-Western Railway'

Kyiv, , Ukraine

Medical Center Health and Happy

Kyiv, , Ukraine

Mnpe 'Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council'

Nove, , Ukraine

Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU

Ternopil, , Ukraine

Zaporizhzhia Regional Clinical Hospital

Zaporizhzhia, , Ukraine

Kingsway Hospital

Derby, , United Kingdom

Synexus

Greater Manchester, , United Kingdom

Garden Valleys Resource Centre

Harrogate, , United Kingdom

Kings College Hospital NHS Trust

London, , United Kingdom

Cornwall Partnership Foundation Trust

Redruth, , United Kingdom

Countries

United States; Argentina; Belgium; Bulgaria; Canada; Czechia; Latvia; Lithuania; Malaysia; Poland; Russia; Serbia; Slovakia; Ukraine; United Kingdom

Other Identifiers

42847922MDD3005

Identifier Type: OTHER

Identifier Source: secondary_id

2020-000341-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108810

Identifier Type: -

Identifier Source: org_study_id