NCT04513912

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).

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
757

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Sep 2020

Typical duration for phase_3

Geographic Reach
15 countries

175 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 13, 2020

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 14, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

September 15, 2020

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 3, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 3, 2023

Completed
Last Updated

August 13, 2025

Status Verified

August 1, 2025

Enrollment Period

3 years

First QC Date

August 13, 2020

Last Update Submit

August 11, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

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

    Responders are defined as percentage of participants with greater than or equal to (\>=) 50 percent (%) improvement in the montgomery-asberg depression rating scale (MADRS) total score from baseline. 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.

    Week 26

Secondary Outcomes (9)

  • 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

  • +4 more secondary outcomes

Study Arms (2)

Seltorexant

EXPERIMENTAL

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.

Drug: SeltorexantDrug: Matching placebo to Seltorexant

Quetiapine Extended-Release (XR)

ACTIVE COMPARATOR

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.

Drug: Quetiapine XRDrug: Matching placebo to Quetiapine XR

Interventions

Participants will receive seltorexant over-encapsulated tablet orally.

Seltorexant

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

Seltorexant

Participants will receive quetiapine XR capsule orally.

Quetiapine Extended-Release (XR)

Participants will receive placebo capsule matching to quetiapine XR orally.

Quetiapine Extended-Release (XR)

Eligibility Criteria

Age18 Years - 74 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (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
  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (175)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

SW Biomedical Research LLC

Tucson, Arizona, 85712, United States

Location

Proscience Research Group

Culver City, California, 90230, United States

Location

Pharmacology Research Institute

Encino, California, 91316, United States

Location

Collaborative NeuroScience Network

Garden Grove, California, 92845, United States

Location

Collaborative NeuroScience Network

Long Beach, California, 90806, United States

Location

Pharmacology Research Institute

Los Alamitos, California, 90720, United States

Location

CalNeuro Research

Los Angeles, California, 90025, United States

Location

Pharmacology Research Institute

Newport Beach, California, 92660, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

Pacific Neuropsychiatric Specialists

Orange, California, 92868, United States

Location

CNRI-Los Angeles, LLC

Pico Rivera, California, 90660, United States

Location

Prospective Research Innovations Inc

Rancho Cucamonga, California, 91730, United States

Location

Anderson Clinical Research

Redlands, California, 92374, United States

Location

University of California at San Diego

San Diego, California, 92103, United States

Location

National Research Institute

Santa Ana, California, 91704, United States

Location

CI Trials

Santa Ana, California, 92705, United States

Location

CMB Clinical Trials

Santee, California, 92071, United States

Location

Schuster Medical Research Institute

Sherman Oaks, California, 91403, United States

Location

Pacific Clinical Research Medical Group

Upland, California, 91786, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Moonshine Research Center, Inc

Doral, Florida, 33166, United States

Location

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, 33009, United States

Location

Indago Research & Health Center Inc

Hialeah, Florida, 33012, United States

Location

New Life Medical Research Center, Inc.

Hialeah, Florida, 33012, United States

Location

Amedica Research Institute Inc

Hialeah, Florida, 33013, United States

Location

Meridien Research

Lakeland, Florida, 33803, United States

Location

Premier Clinical Research

Miami, Florida, 33122, United States

Location

Global Medical Institutes

Miami, Florida, 33125, United States

Location

Miami Jewish Health System

Miami, Florida, 33137, United States

Location

Clinical Neuroscience Solutions

Orlando, Florida, 23801, United States

Location

Synexus Research Orlando

Orlando, Florida, 32806, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Compass Research LLC-Bioclinica Research

The Villages, Florida, 32162, United States

Location

Synexus Clinical Research US Inc

Atlanta, Georgia, 30328, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

iResearch Atlanta LLC

Decatur, Georgia, 30030, United States

Location

Psych Atlanta, P.C.

Marietta, Georgia, 30060, United States

Location

Chicago Research Center

Chicago, Illinois, 60634, United States

Location

Capstone Clinical Research

Libertyville, Illinois, 60048, United States

Location

Alexian Brothers Health System

Lisle, Illinois, 60532, United States

Location

Baber Research Group

Naperville, Illinois, 60563, United States

Location

Lemah Creek Clinical Research

Oakbrook Terrace, Illinois, 60618, United States

Location

Ascension via Christi Research

Wichita, Kansas, 67214, United States

Location

Riverstar Research

New Orleans, Louisiana, 70115, United States

Location

Pharmasite Research, Inc.

Baltimore, Maryland, 21208, United States

Location

BTC of New Bedford

New Bedford, Massachusetts, 02740, United States

Location

Boston Clinical Trials & Medical Research

Roslindale, Massachusetts, 02135, United States

Location

Psychiatric Care and Research Center (PCRC)

O'Fallon, Missouri, 63368, United States

Location

Bio Behavioral Health

Toms River, New Jersey, 08755, United States

Location

SPRI Clinical Trials, LLC

Brooklyn, New York, 11235, United States

Location

Fieve Clinical Research Inc

New York, New York, 10017, United States

Location

The Medical Research Network, LLC

New York, New York, 10128, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618 1609, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Velocity Clinical Research, Inc.

Durham, North Carolina, 27701, United States

Location

University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, 45219, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

Neuro Behavioral Clinical Research

North Canton, Ohio, 44720, United States

Location

Sooner Clinical Research

Oklahoma City, Oklahoma, 73112, United States

Location

Paradigm Research Professionals, LLC

Oklahoma City, Oklahoma, 73118, United States

Location

Suburban Research Associates

Pine Hill, Pennsylvania, 08021, United States

Location

Global Medical Institutes

Scranton, Pennsylvania, 18503, United States

Location

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, 29464, United States

Location

West Houston Clinical Research Service

Bellaire, Texas, 77401, United States

Location

North Texas Clinical Trials

Fort Worth, Texas, 76104, United States

Location

Hawkins Psychiatry, PC

Mansfield, Texas, 76054, United States

Location

Family Psychiatry of The Woodlands

The Woodlands, Texas, 77381, United States

Location

Grayline Research Center

Wichita Falls, Texas, 76309, United States

Location

Alpine Research Organization

Clinton, Utah, 84015, United States

Location

Cedar Clinical Research

Draper, Utah, 84020, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

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

Waukesha, Wisconsin, 53188, United States

Location

CENydET - Centro Neurobiologico y de Stress Traumatico

Buenos Aires, 1058AAJ, Argentina

Location

Hospital Italiano

Buenos Aires, 1199, Argentina

Location

FunDaMos

Buenos Aires, C1405BOA, Argentina

Location

Hospital Fleni

Ciudad Autonoma Buenos Aires, C1428AQK, Argentina

Location

Fundacion Lennox

Córdoba, 5000, Argentina

Location

Instituto Privado Kremer

Córdoba, X5004AOA, Argentina

Location

Centro Medico Luquez

Córdoba, X5006IKK, Argentina

Location

CENPIA

La Plata, 1902, Argentina

Location

Clinica Privada de Salud Mental Santa Teresa de Ávila

La Plata, Thanks, Argentina

Location

CENAIN

Mendoza, M5502AWY, Argentina

Location

Clinica Mayo de UMCB

San Miguel de Tucumán, 4000, Argentina

Location

AZ Sint-Lucas

Bruges, 8310, Belgium

Location

AZ Nikolaas

Sint-Niklaas, 9100, Belgium

Location

Medical Center Medconsult-Pleven

Pleven, 5800, Bulgaria

Location

MC 'Hipokrat - N', EOOD

Plovdiv, 4028, Bulgaria

Location

Mental Health Center - Rousse

Rousse, 7003, Bulgaria

Location

Medical Center St. Naum

Sofia, 1113, Bulgaria

Location

Medical Center Intermedica, OOD

Sofia, 1680, Bulgaria

Location

MC 'Synexus Sofia' EOOD

Sofia, 1784, Bulgaria

Location

MC 'Synexus Sofia' EOOD

Stara Zagora, 6000, Bulgaria

Location

UMHAT Prof. Dr. St. Kirkovich AD

Stara Zagora, 6003, Bulgaria

Location

State Psychiatric Hospital - Tzarev Brod

Tzarev Brod, 9747, Bulgaria

Location

Diagnostic Consulting Center Mladost - M Varna

Varna, 9020, Bulgaria

Location

Mental Health Center - Veliko Tarnovo EOOD

Veliko Tarnovo, 5000, Bulgaria

Location

A.K. Munshi Medical Inc.

Sydney, Nova Scotia, B1P 1E1, Canada

Location

Canadian Phase Onward

Toronto, Ontario, M3J 2C5, Canada

Location

Clinique Force Medic (GCP Trials)

Montreal, Quebec, H1M 1B1, Canada

Location

Psychiatricka ambulance Saint Anne s.r.o.

Brno, 60200, Czechia

Location

NeuropsychiatrieHK, s.r.o.

Hradec Králové, 500 09, Czechia

Location

A Shine S R O

Pilsen, 301 00, Czechia

Location

Clintrial s r o

Prague, 100 00, Czechia

Location

AD71 s.r.o.

Prague, 10000, Czechia

Location

NeuropsychiatrieHK, s.r.o.

Prague, 160 00, Czechia

Location

Institut Neuropsychiatricke pece

Prague, 186 00, Czechia

Location

The Mental Hospital of Jelgava Ģintermuiža - Psychiatry

Jelgava, LV-3008, Latvia

Location

L. Keruze Practice in Psychiatry

Liepāja, LV-3401, Latvia

Location

Hospital of Rezekne

Outpatient Centre of Psychiatry, LV-4601, Latvia

Location

Riga Centre of Psychiatry and Narcology

Riga, LV-1002, Latvia

Location

Kaunas Silainiu Outpatient Clinic, Public Institution

Kaunas, 48259, Lithuania

Location

Republic Kaunas Hospital

Kaunas, 53136, Lithuania

Location

Romuvos Klinika, JSC

Kaunas, LT-44279, Lithuania

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, LT-50009, Lithuania

Location

Medical Center Puriena JSC

Šilutė, 99176, Lithuania

Location

Zirmunai Mental Health Center, Public Institution

Vilnius, 09112, Lithuania

Location

Antakalnis Psychiatric Consultation Centre, Public Institution

Vilnius, 10204, Lithuania

Location

Vilnius Mental Health Center

Vilnius, 10309, Lithuania

Location

Hospital Raja Permaisuri Bainun

Ipoh, 30990, Malaysia

Location

Hospital Permai

Johor Bahru, 81200, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, 10990, Malaysia

Location

Hospital Tuanku Jaafar

Seremban, 70300, Malaysia

Location

Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski

Bełchatów, 97-400, Poland

Location

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

Bialystok, 15-464, Poland

Location

Przychodnia Srodmiescie SP. z o.o.

Bydgoszcz, 85-080, Poland

Location

Centrum Badan Klinicznych PI House sp z o o

Gdansk, 80 546, Poland

Location

Specjalistyczna Indywidualna Praktyka Lekarska

Lodz, 90-009, Poland

Location

CCBR - Lodz - PL

Lodz, 90-368, Poland

Location

Specjalistyczna Praktyka Lekarska Marek Domanski

Lublin, 20-582, Poland

Location

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

Poznan, 60-702, Poland

Location

Specjalistyczny Osrodek Medycyny Wieku Dojrzalego Sp z o.o.

Warsaw, 01 737, Poland

Location

Instytut Psychiatrii I Neurologii

Warsaw, 02 957, Poland

Location

Engels psychiatric hospital

Engel's, 413124, Russia

Location

Kemerovo Regional Clinical Psychiatric Hospital

Kemerovo, 650036, Russia

Location

GUZ Lipetsk Regional psychoneurological Hospital #1

Lipetsk Region, 399313, Russia

Location

JSC Scientific Centre of Personalized Medicine

Moscow, 105082, Russia

Location

FSI Moscow SRI of Psychiatry of Minzdravsocrazvitia

Moscow, 107076, Russia

Location

Moscow Scientific Research Institute of Psychiatry

Moscow, 107076, Russia

Location

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

Omsk, 644070, Russia

Location

St-Petersburg Bekhterev Psychoneurological Research Institute

Saint Petersburg, 192019, Russia

Location

Klinika StoLet Ltd

Tomsk, 634009, Russia

Location

Sverdlov Regional Psychiatric Clinical Hospital

Yekaterinburg, 620030, Russia

Location

General Hospital Acibadem Bel Medic

Belgrade, 11000, Serbia

Location

General Hospital Euromedik

Belgrade, 11000, Serbia

Location

Institute of Mental Health Serbia

Belgrade, 11000, Serbia

Location

University Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

University Clinical Hospital Center Dr Dragisa Misovic- Dedi

Belgrade, 11000, Serbia

Location

Special Neuropsychiatric Hospital Kovin

Kovin, 26220, Serbia

Location

University Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Clinical Center Nis

Niš, 18000, Serbia

Location

Specialized Hospital for Neuropsychiatric Diseases Sveti Vracevi

Novi Kneževac, 23330, Serbia

Location

Psychomed-Svatosavsky, s.r.o.

Banská Bystrica, 97401, Slovakia

Location

Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach

Bojnice, 97201, Slovakia

Location

Epamed sro

Košice, 040 11, Slovakia

Location

Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu

Liptovský Mikuláš, 03123, Slovakia

Location

Psychiatricka Ambulancia Psycholine S.R.O.

Rimavská Sobota, 97901, Slovakia

Location

FN Trencin

Trenčín, 91101, Slovakia

Location

Pro mente sana s.r.o.

Trenčín, 91108, Slovakia

Location

Fakultna nemocnica s poliklinikou v Ziline

Žilina, 1207, Slovakia

Location

MNCE of Kyiv RC Regional Psychiatric and Narcological Medical Association

Hlevakha, 8631, Ukraine

Location

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

Kharkiv, 61068, Ukraine

Location

Kyiv Territorial Medical Incorporation 'Psychiatry'

Kyiv, 04080, Ukraine

Location

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

Kyiv, 1030, Ukraine

Location

Medical Center Health and Happy

Kyiv, 1034, Ukraine

Location

Mnpe 'Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council'

Nove, 25491, Ukraine

Location

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

Ternopil, 46020, Ukraine

Location

Zaporizhzhia Regional Clinical Hospital

Zaporizhzhia, 69600, Ukraine

Location

Kingsway Hospital

Derby, DE22 3LZ, United Kingdom

Location

Synexus

Greater Manchester, M15 6SX, United Kingdom

Location

Garden Valleys Resource Centre

Harrogate, HG1 2PW, United Kingdom

Location

Kings College Hospital NHS Trust

London, SE5 8EF, United Kingdom

Location

Cornwall Partnership Foundation Trust

Redruth, TR15 2SP, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

seltorexant

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental 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 13, 2020

First Posted

August 14, 2020

Study Start

September 15, 2020

Primary Completion

October 3, 2023

Study Completion

October 3, 2023

Last Updated

August 13, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will share

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical- trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu

More information

Locations