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

Depressive Disorder, Major Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04513912
• Other study ID #: CR108810
• Secondary ID: 42847922MDD30052
• Status: Completed
• Phase: Phase 3
• Start date: September 15, 2020
• Est. completion date: October 3, 2023

Study information

• Verified date: December 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 757
• Est. completion date: October 3, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Seltorexant
Participants will receive seltorexant over-encapsulated tablet orally.
• Matching placebo to Seltorexant
Participants will receive placebo over-encapsulated tablet matching to seltorexant orally.
• Quetiapine XR
Participants will receive quetiapine XR capsule orally.
• Matching placebo to Quetiapine XR
Participants will receive placebo capsule matching to quetiapine XR orally.

Locations

Country	Name	City	State
Argentina	CENydET - Centro Neurobiologico y de Stress Traumatico	Buenos Aires
Argentina	Hospital Fleni	Ciudad Autonoma Buenos Aires
Argentina	FunDaMos	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Italiano	Ciudad Autonoma de Buenos Aires
Argentina	Centro Medico Luquez	Cordoba
Argentina	Fundacion Lennox	Cordoba
Argentina	Instituto Privado Kremer	Cordoba
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 Tucuman
Belgium	AZ Sint-Lucas	Brugge
Belgium	AZ Nikolaas	Sint-Niklaas
Bulgaria	Medical Center Medconsult-Pleven	Pleven
Bulgaria	MC 'Hipokrat - N', EOOD	Plovdiv
Bulgaria	Mental Health Center - Rousse	Ruse
Bulgaria	MC 'Synexus Sofia' EOOD	Sofia
Bulgaria	Medical Center Intermedica, OOD	Sofia
Bulgaria	Medical Center St. Naum	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
Canada	Clinique Force Medic (GCP Trials)	Montreal	Quebec
Canada	A.K. Munshi Medical Inc.	Sydney	Nova Scotia
Canada	Canadian Phase Onward	Toronto	Ontario
Czechia	Psychiatricka ambulance Saint Anne s.r.o.	Brno
Czechia	NeuropsychiatrieHK, s.r.o.	Hradec Kralove
Czechia	A-Shine s.r.o.	Plzen
Czechia	AD71 s.r.o.	Praha 10
Czechia	Clintrial s.r.o.	Praha 10
Czechia	NeuropsychiatrieHK, s.r.o.	Praha 6
Czechia	Institut Neuropsychiatricke pece	Praha 8
Latvia	The Mental Hospital of Jelgava Gintermuiža - Psychiatry	Jelgava
Latvia	L. Keruze Practice in Psychiatry	Liepaja
Latvia	Hospital of Rezekne	Outpatient Centre Of Psychiatry
Latvia	Riga Centre of Psychiatry and Narcology	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Kaunas Silainiu Outpatient Clinic, Public Institution	Kaunas
Lithuania	Republic Kaunas Hospital	Kaunas
Lithuania	Romuvos Klinika, JSC	Kaunas
Lithuania	Medical Center Puriena JSC	Silute
Lithuania	Antakalnis Psychiatric Consultation Centre, Public Institution	Vilnius
Lithuania	Vilnius Mental Health Center	Vilnius
Lithuania	Zirmunai Mental Health Center, Public Institution	Vilnius
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh
Malaysia	Hospital Permai	Johor Bahru
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Malaysia	Hospital Tuanku Jaafar	Seremban
Poland	Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski	Belchatow
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	CCBR - Lodz - PL	Lodz
Poland	Specjalistyczna Indywidualna Praktyka Lekarska	Lodz
Poland	Specjalistyczna Praktyka Lekarska Marek Domanski	Lublin
Poland	Synexus Polska Sp. z.o.o. Oddzial w Poznaniu	Poznan
Poland	Instytut Psychiatrii I Neurologii	Warsaw
Poland	Specjalistyczny Osrodek Medycyny Wieku Dojrzalego Sp z o.o.	Warszawa
Russian Federation	Sverdlov Regional Psychiatric Clinical Hospital	Ekaterinburg
Russian Federation	Engels psychiatric hospital	Engels, Saratov Region
Russian Federation	Kemerovo Regional Clinical Psychiatric Hospital	Kemerovo
Russian Federation	GUZ Lipetsk Regional psychoneurological Hospital #1	Lipetsk Region
Russian Federation	FSI Moscow SRI of Psychiatry of Minzdravsocrazvitia	Moscow
Russian Federation	JSC Scientific Centre of Personalized Medicine	Moscow
Russian Federation	Moscow Scientific Research Institute of Psychiatry	Moscow
Russian Federation	Clinical Psychiatry Hospital n.a. N.N. Solodovnikov	Omsk
Russian Federation	St-Petersburg Bekhterev Psychoneurological Research Institute	St. Petersburg
Russian Federation	Klinika StoLet Ltd	Tomsk
Serbia	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	Nis
Serbia	Specialized Hospital for Neuropsychiatric Diseases Sveti Vracevi	Novi Knezevac
Slovakia	Psychomed-Svatosavsky, s.r.o.	Banska Bystrica
Slovakia	Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach	Bojnice
Slovakia	Epamed sro	Koshice
Slovakia	Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu	Liptovsky Mikulas
Slovakia	Psychiatricka Ambulancia Psycholine S.R.O.	Rimavska Sobota
Slovakia	FN Trencin	Trencin
Slovakia	Pro mente sana s.r.o.	Trencin
Slovakia	Fakultna nemocnica s poliklinikou v Ziline	Zilina
Ukraine	MNCE of Kyiv RC Regional Psychiatric and Narcological Medical Association	Glevakha
Ukraine	Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'	Kharkiv
Ukraine	Kyiv Territorial Medical Incorporation 'Psychiatry'	Kyiv
Ukraine	Medical Center Health and Happy	Kyiv
Ukraine	Railway Clinical Hospital #1 of Kiev Railway station of DTGO 'South-Western Railway'	Kyiv
Ukraine	Mnpe 'Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council'	Nove, Kropyvnytskiy
Ukraine	Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU	Ternopil
Ukraine	Zaporizhzhia Regional Clinical Hospital	Zaporizhzhia
United Kingdom	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 States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Synexus Clinical Research US, Inc	Atlanta	Georgia
United States	Pharmasite Research, Inc.	Baltimore	Maryland
United States	West Houston Clinical Research Service	Bellaire	Texas
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	SPRI Clinical Trials, LLC	Brooklyn	New York
United States	University of Virginia	Charlottesville	Virginia
United States	Chicago Research Center	Chicago	Illinois
United States	University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience	Cincinnati	Ohio
United States	Alpine Research Organization	Clinton	Utah
United States	Proscience Research Group	Culver City	California
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	iResearch Atlanta LLC	Decatur	Georgia
United States	Moonshine Research Center, Inc	Doral	Florida
United States	Cedar Clinical Research	Draper	Utah
United States	Velocity Clinical Research, Inc.	Durham	North Carolina
United States	Pharmacology Research Institute	Encino	California
United States	Core Clinical Research	Everett	Washington
United States	North Texas Clinical Trials	Fort Worth	Texas
United States	Collaborative NeuroScience Network	Garden Grove	California
United States	Velocity Clinical Research, Hallandale Beach	Hallandale Beach	Florida
United States	Hartford Hospital	Hartford	Connecticut
United States	Amedica Research Institute, Inc.	Hialeah	Florida
United States	Indago Research & Health Center Inc	Hialeah	Florida
United States	New Life Medical Research Center, Inc.	Hialeah	Florida
United States	Meridien Research	Lakeland	Florida
United States	Capstone Clinical Research	Libertyville	Illinois
United States	Alexian Brothers Health System	Lisle	Illinois
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	Hawkins Psychiatry, PC	Mansfield	Texas
United States	Psych Atlanta, P.C.	Marietta	Georgia
United States	Global Medical Institutes	Miami	Florida
United States	Miami Jewish Health System	Miami	Florida
United States	Premier Clinical Research	Miami	Florida
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	Baber Research Group	Naperville	Illinois
United States	BTC of New Bedford	New Bedford	Massachusetts
United States	Riverstar Research	New Orleans	Louisiana
United States	Fieve Clinical Research, Inc.	New York	New York
United States	The Medical Research Network, LLC	New York	New York
United States	Pharmacology Research Institute	Newport Beach	California
United States	Neuro-Behavioral Clinical Research	North Canton	Ohio
United States	Psychiatric Care and Research Center (PCRC)	O'Fallon	Missouri
United States	Lemah Creek Clinical Research	Oakbrook Terrace	Illinois
United States	Paradigm Research Professionals, LLC	Oklahoma City	Oklahoma
United States	Sooner Clinical Research	Oklahoma City	Oklahoma
United States	NRC Research Institute	Orange	California
United States	Pacific Neuropsychiatric Specialists	Orange	California
United States	Clinical Neuroscience Solutions	Orlando	Florida
United States	Synexus Research Orlando	Orlando	Florida
United States	CNRI-Los Angeles, LLC	Pico Rivera	California
United States	Suburban Research Associates	Pine Hill	Pennsylvania
United States	Prospective Research Innovations, Inc.	Rancho Cucamonga	California
United States	Anderson Clinical Research	Redlands	California
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Boston Clinical Trials & Medical Research	Roslindale	Massachusetts
United States	University of California at San Diego	San Diego	California
United States	CI Trials	Santa Ana	California
United States	National Research Institute	Santa Ana	California
United States	CMB Clinical Trials	Santee	California
United States	Global Medical Institutes	Scranton	Pennsylvania
United States	Schuster Medical Research Institute	Sherman Oaks	California
United States	Richmond Behavioral Associates	Staten Island	New York
United States	University of South Florida	Tampa	Florida
United States	Compass Research LLC-Bioclinica Research	The Villages	Florida
United States	Family Psychiatry of The Woodlands	The Woodlands	Texas
United States	Bio Behavioral Health	Toms River	New Jersey
United States	SW Biomedical Research, LLC	Tucson	Arizona
United States	Pacific Clinical Research Medical Group	Upland	California
United States	Cary J. Kohlenberg, MD, SC, dba, IPC Research.	Waukesha	Wisconsin
United States	Ascension via Christi Research	Wichita	Kansas
United States	Grayline Research Center	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bulgaria,  Canada,  Czechia,  Latvia,  Lithuania,  Malaysia,  Poland,  Russian Federation,  Serbia,  Slovakia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline in Weight up to Week 26	Change from baseline in weight will be reported.	Baseline to Week 26
Secondary	Time to Study Drug Discontinuation for Potentially Treatment Related Reasons	Time to discontinuation of study drug for potentially treatment related reasons will be reported. Potentially treatment related reasons are defined as all study drug discontinuations excluding the potentially non-treatment related discontinuations (eg, loss of insurance for antidepressant therapy, movement/travel out of the area, change of work-schedule being unable to accommodate visit schedule, family circumstances).	Up to Week 26
Secondary	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 to Week 26
Secondary	Change from Baseline in MADRS-6 Total Score	The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).	Baseline to Week 26
Secondary	Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score	The MADRS is a 10-item clinician-rated instrument for evaluating severity of symptoms of depression. Each item is rated on a scale from 0 to 6, with higher scores indicating greater symptom severity. MADRS-WOSI considered 9 of the 10 MADRS items, excluding "reduced sleep" item. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity.	Baseline to Week 26
Secondary	Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score	The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the diagnostic and statistical manual of mental disorders-5th edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.	Baseline to Week 26
Secondary	Percentage of Participants with Remission (MADRS Total Score less than or equal to (<=) 12) at Week 26	Percentage of participants with remission (MADRS total Score <=12) will be reported.	Week 26
Secondary	Percentage of Participants with a >=50 Percent Improvement in MADRS Total Score and MADRS <=18 at Week 26	Percentage of participants with a >=50 percent improvement in MADRS total score and MADRS <=18 at Week 26.	Week 26
Secondary	Percentage of Participants with Weight Increase >=7 Percent from Baseline at Week 26	Percentage of participants with weight increase >=7 percent from baseline will be reported.	Week 26