Clinical trial NCT04513912: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-08-14
Enrollment: 757
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants with Response (>=50 Percent improvement in MADRS total score from baseline) at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Change from baseline in Weight up to Week 26
timeFrame: Baseline to Week 26
measure: Time to Study Drug Discontinuation for Potentially Treatment Related Reasons
timeFrame: Up to Week 26
measure: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline to Week 26
measure: Change from Baseline in MADRS-6 Total Score
timeFrame: Baseline to Week 26
measure: Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score
timeFrame: Baseline to Week 26
measure: Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score
timeFrame: Baseline to Week 26
measure: Percentage of Participants with Remission (MADRS Total Score less than or equal to (<=) 12) at Week 26
timeFrame: Week 26
measure: Percentage of Participants with a >=50 Percent Improvement in MADRS Total Score and MADRS <=18 at Week 26
timeFrame: Week 26
measure: Percentage of Participants with Weight Increase >=7 Percent from Baseline at Week 26
timeFrame: Week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: SW Biomedical Research LLC
state: Arizona
city: Culver City
country: United States
facility: Proscience Research Group
state: California
city: Encino
country: United States
facility: Pharmacology Research Institute
state: California
city: Garden Grove
country: United States
facility: Collaborative NeuroScience Network
state: California
city: Long Beach
country: United States
facility: Collaborative NeuroScience Network
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Los Angeles
country: United States
facility: CalNeuro Research
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Orange
country: United States
facility: Pacific Neuropsychiatric Specialists
state: California
city: Pico Rivera
country: United States
facility: CNRI-Los Angeles, LLC
state: California
city: Rancho Cucamonga
country: United States
facility: Prospective Research Innovations Inc
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Santa Ana
country: United States
facility: National Research Institute
state: California
city: Santa Ana
country: United States
facility: CI Trials
state: California
city: Santee
country: United States
facility: CMB Clinical Trials
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Medical Group
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Doral
country: United States
facility: Moonshine Research Center, Inc
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center Inc
state: Florida
city: Hialeah
country: United States
facility: New Life Medical Research Center, Inc.
state: Florida
city: Hialeah
country: United States
facility: Amedica Research Institute Inc
state: Florida
city: Lakeland
country: United States
facility: Meridien Research
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research
state: Florida
city: Miami
country: United States
facility: Global Medical Institutes
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health System
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Orlando
country: United States
facility: Synexus Research Orlando
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: The Villages
country: United States
facility: Compass Research LLC-Bioclinica Research
state: Florida
city: Atlanta
country: United States
facility: Synexus Clinical Research US Inc
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta LLC
state: Georgia
city: Marietta
country: United States
facility: Psych Atlanta, P.C.
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Libertyville
country: United States
facility: Capstone Clinical Research
state: Illinois
city: Lisle
country: United States
facility: Alexian Brothers Health System
state: Illinois
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Lemah Creek Clinical Research
state: Illinois
city: Wichita
country: United States
facility: Ascension via Christi Research
state: Kansas
city: New Orleans
country: United States
facility: Riverstar Research
state: Louisiana
city: Baltimore
country: United States
facility: Pharmasite Research, Inc.
state: Maryland
city: New Bedford
country: United States
facility: BTC of New Bedford
state: Massachusetts
city: Roslindale
country: United States
facility: Boston Clinical Trials & Medical Research
state: Massachusetts
city: O'Fallon
country: United States
facility: Psychiatric Care and Research Center (PCRC)
state: Missouri
city: Toms River
country: United States
facility: Bio Behavioral Health
state: New Jersey
city: Brooklyn
country: United States
facility: SPRI Clinical Trials, LLC
state: New York
city: New York
country: United States
facility: Fieve Clinical Research Inc
state: New York
city: New York
country: United States
facility: The Medical Research Network, LLC
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Durham
country: United States
facility: Velocity Clinical Research, Inc.
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: North Canton
country: United States
facility: Neuro Behavioral Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals, LLC
state: Oklahoma
city: Pine Hill
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Scranton
country: United States
facility: Global Medical Institutes
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Bellaire
country: United States
facility: West Houston Clinical Research Service
state: Texas
city: Fort Worth
country: United States
facility: North Texas Clinical Trials
state: Texas
city: Mansfield
country: United States
facility: Hawkins Psychiatry, PC
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Research Center
state: Texas
city: Clinton
country: United States
facility: Alpine Research Organization
state: Utah
city: Draper
country: United States
facility: Cedar Clinical Research
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Waukesha
country: United States
facility: Cary J. Kohlenberg, MD, SC, dba, IPC Research.
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: CENydET - Centro Neurobiologico y de Stress Traumatico
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Fleni
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: FunDaMos
city: Cordoba
country: Argentina
facility: Fundacion Lennox
city: Cordoba
country: Argentina
facility: Instituto Privado Kremer
city: Cordoba
country: Argentina
facility: Centro Medico Luquez
city: La Plata
country: Argentina
facility: CENPIA
city: La Plata
country: Argentina
facility: Clinica Privada de Salud Mental Santa Teresa de Ávila
city: Mendoza
country: Argentina
facility: CENAIN
city: San Miguel de Tucuman
country: Argentina
facility: Clinica Mayo de UMCB
city: Brugge
country: Belgium
facility: AZ Sint-Lucas
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult-Pleven
city: Plovdiv
country: Bulgaria
facility: MC 'Hipokrat - N', EOOD
city: Ruse
country: Bulgaria
facility: Mental Health Center - Rousse
city: Sofia
country: Bulgaria
facility: Medical Center St. Naum
city: Sofia
country: Bulgaria
facility: Medical Center Intermedica, OOD
city: Sofia
country: Bulgaria
facility: MC 'Synexus Sofia' EOOD
city: Stara Zagora
country: Bulgaria
facility: MC 'Synexus Sofia' EOOD
city: Stara Zagora
country: Bulgaria
facility: UMHAT Prof. Dr. St. Kirkovich AD
city: Tzarev Brod
country: Bulgaria
facility: State Psychiatric Hospital - Tzarev Brod
city: Varna
country: Bulgaria
facility: Diagnostic Consulting Center Mladost - M Varna
city: Veliko Tarnovo
country: Bulgaria
facility: Mental Health Center - Veliko Tarnovo EOOD
city: Sydney
country: Canada
facility: A.K. Munshi Medical Inc.
state: Nova Scotia
city: Toronto
country: Canada
facility: Canadian Phase Onward
state: Ontario
city: Montreal
country: Canada
facility: Clinique Force Medic (GCP Trials)
state: Quebec
city: Brno
country: Czechia
facility: Psychiatricka ambulance Saint Anne s.r.o.
city: Hradec Kralove
country: Czechia
facility: NeuropsychiatrieHK, s.r.o.
city: Plzen
country: Czechia
facility: A Shine S R O
city: Praha 10
country: Czechia
facility: Clintrial s r o
city: Praha 10
country: Czechia
facility: AD71 s.r.o.
city: Praha 6
country: Czechia
facility: NeuropsychiatrieHK, s.r.o.
city: Praha 8
country: Czechia
facility: Institut Neuropsychiatricke pece
city: Jelgava
country: Latvia
facility: The Mental Hospital of Jelgava Ģintermuiža - Psychiatry
city: Liepaja
country: Latvia
facility: L. Keruze Practice in Psychiatry
city: Outpatient Centre Of Psychiatry
country: Latvia
facility: Hospital of Rezekne
city: Riga
country: Latvia
facility: Riga Centre of Psychiatry and Narcology
city: Kaunas
country: Lithuania
facility: Kaunas Silainiu Outpatient Clinic, Public Institution
city: Kaunas
country: Lithuania
facility: Republic Kaunas Hospital
city: Kaunas
country: Lithuania
facility: Romuvos Klinika, JSC
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Silute
country: Lithuania
facility: Medical Center Puriena JSC
city: Vilnius
country: Lithuania
facility: Zirmunai Mental Health Center, Public Institution
city: Vilnius
country: Lithuania
facility: Antakalnis Psychiatric Consultation Centre, Public Institution
city: Vilnius
country: Lithuania
facility: Vilnius Mental Health Center
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Johor Bahru
country: Malaysia
facility: Hospital Permai
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Seremban
country: Malaysia
facility: Hospital Tuanku Jaafar
city: Belchatow
country: Poland
facility: Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski
city: Bialystok
country: Poland
facility: Wlokiennicza MED Specjalistyczna Praktyka Lekarska dr n.med. Tomasz Markowski
city: Bydgoszcz
country: Poland
facility: Przychodnia Srodmiescie SP. z o.o.
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI House sp z o o
city: Lodz
country: Poland
facility: Specjalistyczna Indywidualna Praktyka Lekarska
city: Lodz
country: Poland
facility: CCBR - Lodz - PL
city: Lublin
country: Poland
facility: Specjalistyczna Praktyka Lekarska Marek Domanski
city: Poznan
country: Poland
facility: Synexus Polska Sp. z.o.o. Oddzial w Poznaniu
city: Warsaw
country: Poland
facility: Instytut Psychiatrii I Neurologii
city: Warszawa
country: Poland
facility: Specjalistyczny Osrodek Medycyny Wieku Dojrzalego Sp z o.o.
city: Ekaterinburg
country: Russian Federation
facility: Sverdlov Regional Psychiatric Clinical Hospital
city: Engels
country: Russian Federation
facility: Engels psychiatric hospital
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Psychiatric Hospital
city: Lipetsk Region
country: Russian Federation
facility: GUZ Lipetsk Regional psychoneurological Hospital #1
city: Moscow
country: Russian Federation
facility: JSC Scientific Centre of Personalized Medicine
city: Moscow
country: Russian Federation
facility: FSI Moscow SRI of Psychiatry of Minzdravsocrazvitia
city: Moscow
country: Russian Federation
facility: Moscow Scientific Research Institute of Psychiatry
city: Omsk
country: Russian Federation
facility: Clinical Psychiatry Hospital n.a. N.N. Solodovnikov
city: St. Petersburg
country: Russian Federation
facility: St-Petersburg Bekhterev Psychoneurological Research Institute
city: Tomsk
country: Russian Federation
facility: Klinika StoLet Ltd
city: Belgrade
country: Serbia
facility: General Hospital Acibadem Bel Medic
city: Belgrade
country: Serbia
facility: General Hospital Euromedik
city: Belgrade
country: Serbia
facility: Institute of Mental Health Serbia
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: University Clinical Hospital Center Dr Dragisa Misovic- Dedi
city: Kovin
country: Serbia
facility: Special Neuropsychiatric Hospital Kovin
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Nis
country: Serbia
facility: Clinical Center Nis
city: Novi Knezevac
country: Serbia
facility: Specialized Hospital for Neuropsychiatric Diseases Sveti Vracevi
city: Banska Bystrica
country: Slovakia
facility: Psychomed-Svatosavsky, s.r.o.
city: Bojnice
country: Slovakia
facility: Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach
city: Koshice
country: Slovakia
facility: Epamed sro
city: Liptovsky Mikulas
country: Slovakia
facility: Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu
city: Rimavska Sobota
country: Slovakia
facility: Psychiatricka Ambulancia Psycholine S.R.O.
city: Trencin
country: Slovakia
facility: FN Trencin
city: Trencin
country: Slovakia
facility: Pro mente sana s.r.o.
city: Zilina
country: Slovakia
facility: Fakultna nemocnica s poliklinikou v Ziline
city: Glevakha
country: Ukraine
facility: MNCE of Kyiv RC Regional Psychiatric and Narcological Medical Association
city: Kharkiv
country: Ukraine
facility: Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'
city: Kyiv
country: Ukraine
facility: Kyiv Territorial Medical Incorporation 'Psychiatry'
city: Kyiv
country: Ukraine
facility: Railway Clinical Hospital #1 of Kiev Railway station of DTGO 'South-Western Railway'
city: Kyiv
country: Ukraine
facility: Medical Center Health and Happy
city: Nove
country: Ukraine
facility: Mnpe 'Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council'
city: Ternopil
country: Ukraine
facility: Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU
city: Zaporizhzhia
country: Ukraine
facility: Zaporizhzhia Regional Clinical Hospital
city: Derby
country: United Kingdom
facility: Kingsway Hospital
city: Greater Manchester
country: United Kingdom
facility: Synexus
city: Harrogate
country: United Kingdom
facility: Garden Valleys Resource Centre
city: London
country: United Kingdom
facility: Kings College Hospital NHS Trust
city: Redruth
country: United Kingdom
facility: Cornwall Partnership Foundation Trust
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: