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

A Multicenter, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Study 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 and an Open-labeled Long-term Safety Extension Treatment With Seltorexant

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Seltorexant; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 588
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil, 30150-270
    • CPN - Centro de Pesquisa em Neurociências Ltda
  • Brasília, Brazil, 70200-730
    • CCB Centro Cardiologico de Brasilia Ltda - CCB Cardiologia
  • Curitiba, Brazil, 81210-310
    • Instituto de Neurologia de Curitiba
  • Fortaleza, Brazil, 60430-380
    • Universidade Federal do Ceara Hospital Universitario Walter Cantidio
  • Passo Fundo, Brazil, 99010-120
    • Instituto Méderi de Pesquisa e Saúde
  • Rio de Janeiro, Brazil, 22270 060
    • Ruschel Medicina e Pesquisa Clínica Ltda
  • São Paulo, Brazil, 04037-003
    • SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
  • São Paulo, Brazil, 13970-905
    • Instituto Bairral de Psiquiatria
• Bulgaria
  • Burgas, Bulgaria, 8001
    • Mental Health Center Prof. Dr. Ivan Temkov
  • Cherven Bryag, Bulgaria, 5980
    • Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET
  • Kardzhali, Bulgaria, 6600
    • State Psychiatric Hospital Kardzhali
  • Plovdiv, Bulgaria, 4000
    • UMHAT 'Sv. Georgi' EAD
  • Plovdiv, Bulgaria, 4000
    • Medical center Spectar - Plovdiv EOOD
  • Slivnitsa, Bulgaria, 1202
    • MHC - Sofia, EOOD
  • Sofia, Bulgaria, 1408
    • DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD
  • Sofia, Bulgaria, 1680
    • Medical Center Intermedica, OOD
  • Sofia, Bulgaria, 1113
    • Medical Center St. Naum
  • Targovishte, Bulgaria, 7700
    • Medical center - VAS OOD
  • Vratsa, Bulgaria, 3000
    • Mental Health Center - Vratsa EOOD
• Colombia
  • Barranquilla, Colombia
    • Centro de Investigaciones y Proyectos en Neurociencias CIPNA
  • Bello, Colombia, 051053
    • HOMO - ESE Hospital Mental de Antioquia
  • Bogotá, Colombia, 111166
    • Centro de Investigaciones del Sistema Nervioso Grupo Cisne Ltda.
  • Medellín, Colombia
    • Fundacion Centro de Investigacion Clinica CIC
  • Pereira, Colombia
    • Psynapsis Salud Mental S.A.
• Czechia
  • Kladno, Czechia, 27201
    • Brain-Soultherapy s.r.o.
  • Kutná Hora, Czechia, 284 01
    • Neuroterapie KH S R O
  • Pilsen, Czechia, 31200
    • A Shine S R O
  • Prague, Czechia, 16000
    • Medical Services Prague S R O
  • Prague, Czechia, 10000
    • Clintrial s r o
• Mexico
  • Monterrey, Mexico, 64310
    • Iecsi S.C.
  • Nuevo León, Mexico, 64060
    • CRI Centro Regiomontano de Investigacion SC
  • San Luis Potosí City, Mexico, 78213
    • BIND Investigaciones S.C.
• Russia
  • Saint Petersburg, Russia, 190013
    • Psychoneurological Dispensary of Frunzensky District
  • Saint Petersburg, Russia, 190020
    • SPb SBIH 'City Psychoneurological Dispensary # 7 (With Inpatient Facilities)'
  • Saint Petersburg, Russia, 190121
    • City Psychiatric Hospital of St. Nikolay Chudotvorets
  • Saint Petersburg, Russia, 192019
    • Bekhterev Psychoneurological Research Institute
  • Saint Petersburg, Russia, 192019
    • St-Petersburg Bekhterev Psychoneurological Research Institute
  • Saint Petersburg, Russia, 199106
    • Psychoneurological dispensary 1
  • Stavropol, Russia, 357034
    • Stavropol Region Psychiatric Hospital #2
  • Yaroslavl, Russia, 150003
    • Yaroslavl Region Clinical Psychiatric Hospital
• South Africa
  • Bloemfontein, South Africa, 9301
    • Farmovs Pty Ltd
  • Bloemfontein, South Africa, 9324
    • Iatros International
  • Cape Town, South Africa, 7530
    • Cape Town Clinical Research Centre
  • Cape Town, South Africa, 7530
    • Flexivest 14 Research
  • Krugersdorp, South Africa, 1739
    • DJW Research
  • Mamelodi East, South Africa, 0122
    • Stanza Clinical Research Centre : Mamelodi
  • Pretoria, South Africa
    • Synexus Watermeyer
  • Strand, South Africa, 7140
    • Somerset West Clinical Research Unit
• Spain
  • Barcelona, Spain, 08025
    • Institucion Hosp Hestia Palau
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Bilbao, Spain, 48013
    • Hosp. Univ. de Basurto
  • Madrid, Spain, 28034
    • Hosp. Univ. Ramon Y Cajal
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Oviedo, Spain, 33011
    • Centro Salud Mental La Corredoria
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Sabadell, Spain, 08208
    • Corporacio Sanitari Parc Tauli
  • Salamanca, Spain, 37005
    • Centro de salud San Juan - IBSAL
  • Zamora, Spain, 49021
    • Hosp. Prov. de Zamora
• Sweden
  • Halmstad, Sweden, SE-30248
    • Affecta Pskyiatrimottagning
  • Helsingborg, Sweden, 25220
    • PharmaSite Helsingborg
  • Lund, Sweden, 22222
    • ProbarE i Lund AB
  • Malmö, Sweden, 21152
    • PharmaSite
  • Skövde, Sweden, 54143
    • Läkarmottagningen
  • Stockholm, Sweden, 111 37
    • ProbarE i Solna
• Taiwan
  • Keelung, Taiwan, 204
    • Chang-Gung Memorial Hospital-Keelung
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 110
    • Taipei Medical University
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 112
    • Cheng Hsin General Hospital
  • Taoyuan County, Taiwan, 33305
    • Chang Gung Memorial Hospital- Linkou
• United States
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center Inc
    • Cerritos, California, United States, 90703
      • Synexus
    • Irvine, California, United States, 92614
      • Irvine Clinical Research
    • La Habra, California, United States, 90631
      • Omega Clinical Trials LLC
    • Lemon Grove, California, United States, 91945
      • Synergy East
    • Los Angeles, California, United States, 90048
      • Semel Institute for Neuroscience and Human Behavior
    • Montclair, California, United States, 91763
      • Catalina Research Institute
    • Oakland, California, United States, 94607
      • Pacific Research Partners
    • Oceanside, California, United States, 92056
      • North County Clinical Research
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Temecula, California, United States, 92591
      • Viking Pharmaceutical Trials Inc. dba Viking Clinical Research
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Connecticut Clinical Trials LLC
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
  • Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions Inc
    • Miami, Florida, United States, 33134
      • Medical Research Center of Miami II Inc
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic Inc
    • Miami, Florida, United States, 33165
      • Phoenix Medical Research, Inc.
    • Miami Springs, Florida, United States, 33166
      • Galiz Research
    • North Bay Village, Florida, United States, 33141
      • Bravo Health Care Center
    • Orlando, Florida, United States, 32803
      • APG Research LLC
    • Orlando, Florida, United States, 32803
      • Combined Research Orlando
    • Orlando, Florida, United States, 32803
      • Nova Psychiatry INC
  • Illinois
    • Elgin, Illinois, United States, 60123
      • Revive Research Institute
    • Joliet, Illinois, United States, 60435
      • Joliet Center for Clinical Research
    • Naperville, Illinois, United States, 60563
      • Baber Research Group
    • Oak Brook, Illinois, United States, 60523
      • American Medical Research, Inc.
    • Springfield, Illinois, United States, 62701
      • Southern Illinois University School of Medicine
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Louisiana Clinical Research
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • NeuroBehavioral Medicine Group
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Midwest Research Group - St. Charles Psychiatric Associates
    • St Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
    • St Louis, Missouri, United States, 63109
      • Mid-America Clinical Research, LLC
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Research Institute, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research Institute
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute, LLC.
  • New York
    • Jamaica, New York, United States, 11432
      • Synexus Clinical Research US Inc
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research LLC
  • Ohio
    • Avon Lake, Ohio, United States, 44012
      • Haidar Almhana Nieding
    • Columbus, Ohio, United States, 43221
      • The Ohio State University
    • Mason, Ohio, United States, 45040
      • Lindner Center of Hope
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma Clinical Research Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Perelman School of Medicine
  • Texas
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials
    • Fort Worth, Texas, United States, 76104
      • North Texas Clinical Trials
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates
  • Utah
    • Clinton, Utah, United States, 84015
      • Alpine Research Organization
  • Vermont
    • Rutland, Vermont, United States, 05701
      • Green Mountain Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Seltorexant; Seltorexant tablet will be administered orally once daily.; Other Names: JNJ-42847922
Placebo Comparator: Placebo; Participants will receive matching placebo tablet orally once daily, from Day 1 to Day 42 in double blind (DB) treatment phase.	Drug: Placebo; Matching placebo tablet will be administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double Blind (DB) Treatment Phase: Change From Baseline to Day 43 in Montgomery- Asberg Depression Rating Scale (MADRS) Total Score- Estimand 1	The MADRS is a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant intervention. Scale has 10 items(apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts) each of which was scored from 0 (not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is sum of scores from individual question items, which ranged from 0 to 60. Higher scores indicates more severe condition. Negative changes in MADRS total score indicates improvement.	Baseline (Day 1), Day 43
Open Label (OL) Treatment Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study drug. Treatment emergent AEs was defined as any AE occurred at or after the initial administration of study intervention through the day of last dose plus 2 days.	From start of the treatment in OL phase (OL Day 1 [Day 43 from study baseline]) up to 2 days after last dose in OL phase (up to 52.28 weeks)
OL Treatment Phase: Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESI)	AE was defined as any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study drug. Treatment emergent AEs was defined as any AE occurred at or after the initial administration of study intervention through the day of last dose plus 2 days. The AEs considered to be of special interest: cataplexy, sleep paralysis, complex, sleep-related behaviors/parasomnias such as confusional arousals, somnambulism, sleep terrors, bruxism, sleep sex, sleep-related eating disorder, and catathrenia, fall, motor vehicle accident.	From start of the treatment in OL phase (OL Day 1 [Day 43 from study baseline]) up to 2 days after last dose in OL phase (up to 52.28 weeks)
OL Treatment Phase: Change From Baseline in Vital Signs: Blood Pressure	Change from baseline in vital signs: systolic/diastolic blood pressure were reported. Blood pressure measurements were assessed with the participant in a sitting position using a completely automated device.	OL Baseline (OL Day 1 [Day 43 from study baseline]) and Week 52
OL Treatment Phase: Change From Baseline: Body Mass Index (BMI)	Change from baseline in BMI were reported.	OL Baseline (OL Day 1 [Day 43 from study baseline]) and Week 52
OL Treatment Phase: Change From Baseline in Vital Signs: Temperature	Change from baseline in vital signs: temperature were reported.	OL Baseline (OL Day 1 [Day 43 from study baseline]) and Week 52
OL Treatment Phase: Change From Baseline in Vital Signs: Pulse Rate	Change from baseline in vital signs: pulse rate were reported. Pulse rate measurements were assessed with the participant in a sitting position using a completely automated device.	OL Baseline (OL Day 1 [Day 43 from study baseline]) and Week 52
OL Treatment Phase: Change From Baseline in Weight	Change from baseline in weight was reported.	OL Baseline (OL Day 1 [Day 43 from study baseline]) and Week 52
OL Treatment Phase: Change From Baseline in Waist Circumference	Change from baseline in waist circumference were reported.	OL Baseline (OL Day 1 [Day 43 from study baseline]) and Week 52
OL Treatment Phase: Number of Participants With Shift From Baseline in Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)	C-SSRS is a clinician-rated instrument that reports severity and frequency of suicide-related ideation and behaviors. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (non-specific active suicidal thoughts), 3 (suicidal ideation without plan and intent), 4 (suicidal ideation intent to act without plan), and 5 (suicidal ideation with plan and intent), Suicidal behavior is classified on a 5-item scale: 6 (preparatory acts or behavior), 7 (aborted attempt), 8 (interrupted attempt), 9 (actual attempt), and 10 (suicide). Total score from 10 categories was summarized into 3 categories: No suicidal ideation or behavior(0), suicidal ideation (1-5), suicidal behavior (6-10). Total score ranged from 0 to 10, higher total scores indicate more suicidal ideation and/or suicidal behavior. Categories with at least 1 non-zero data values are reported.	From DB Baseline (Day 1) up to Week 52
OL Follow Up Phase: Physician Withdrawal Checklist (PWC-20) Total Scores at Start of OL Follow Up	The PWC-20 was a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 was a reliable and sensitive instrument for the assessment of discontinuation symptoms. The assessment has 20 items (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue, poor coordination, restlessness, diaphoresis, tremor, dizziness, headaches, muscle aches or stiffness, weakness, increased acuity sound smell touch, paresthesia, difficulty concentrating-remember, depersonalization-derealization) evaluated to detect withdrawal symptoms. Symptoms are rated on a scale: 0-3, 0 =not present, 1=mild, 2 =moderate, and 3 =severe. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. The higher score indicates more severe symptoms.	Start of OL Follow Up (Week 52)
OL Follow Up Phase: Physician Withdrawal Checklist (PWC-20) Total Scores at Follow up Visit 1	The PWC-20 was a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 was a reliable and sensitive instrument for the assessment of discontinuation symptoms. The assessment has 20 items (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue, poor coordination, restlessness, diaphoresis, tremor, dizziness, headaches, muscle aches or stiffness, weakness, increased acuity sound smell touch, paresthesia, difficulty concentrating-remember, depersonalization-derealization) evaluated to detect withdrawal symptoms. Symptoms are rated on a scale: 0-3, 0 =not present, 1=mild, 2 =moderate, and 3 =severe. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. The higher score indicates more severe symptoms.	Follow up Visit 1: 1 day after end of OL phase (Week 52.14)
OL Follow Up Phase: Physician Withdrawal Checklist (PWC-20) Total Scores at Follow up Visit 2	The PWC-20 was a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 was a reliable and sensitive instrument for the assessment of discontinuation symptoms. The assessment has 20 items (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue, poor coordination, restlessness, diaphoresis, tremor, dizziness, headaches, muscle aches or stiffness, weakness, increased acuity sound smell touch, paresthesia, difficulty concentrating-remember, depersonalization-derealization)evaluated to detect withdrawal symptoms. Symptoms are rated on a scale: 0-3, 0 =not present, 1=mild, 2 =moderate, and 3 =severe. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. The higher score indicates more severe symptoms.	Follow Up Visit 2: 2 weeks after end of OL phase (Week 54)
OL Treatment Phase: Number of Participants With Electrocardiogram (ECG) Abnormalities	Number of participants with ECG abnormalities during OL treatment phase was reported. ECG abnormalities were assessed as per investigator's discretion.	Week 52
OL Treatment Phase: Number of Participants With Clinically Significant Laboratory Abnormalities	Laboratory parameters: hematology (platelet count, red blood cell [RBC] count, hemoglobin, hematocrit, neutrophils (Segmented/Leukocytes), lymphocytes, monocytes, eosinophils/leukocytes [Eos/Leu], basophils, Reticulocytes/ Erythrocytes [Reti/Ery]); chemistry (sodium, potassium, chloride, bicarbonate, creatinine, Creatine Kinase, glucose, aspartate transaminase [AST], alanine transaminase [ALT], gamma-glutamyl transferase [GGT], alkaline phosphatase, total bilirubin, phosphate, albumin, total protein, total cholesterol, high-density lipoprotein, low-density lipoprotein, Triglycerides); urine (specific gravity, pH, glucose, blood, bilirubin, urobilinogen, RBC). Clinically significant abnormalities (low/high) were determined at the investigator's discretion. Only those categories in which at least one participant had data were reported in this outcome measure.	From DB Baseline (Day 1) to Week 52
OL Treatment Phase: Number of Participants With Sexual Dysfunction as Determined by Arizona Sexual Experiences Scale (ASEX) Score	ASEX is a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each of the 5 items is rated on a 6-point Likert scale, ranging from 1 to 6. The 5 items are summed to create a total score, ranging from 5 to 30, with the higher scores indicating more sexual dysfunction. Sexual dysfunction is defined as an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Treatment Phase: Change From Baseline to Day 43 in the MADRS Without Sleep Item (MADRS-WOSI) Total Score- Estimand 1	The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. MADRS-WOSI was defined as the full MADRS without the sleep item. The MADRS-WOSI scale consisted of 9 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS-WOSI total score was the sum of scores from individual question items, which ranged from 0 to 54, higher scores represented a more severe condition. The MADRS-WOSI evaluated apparent sadness, reported sadness, inner tension, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Negative change in MADRS total score indicated improvement.	Baseline (Day 1), Day 43
DB Treatment Phase: Change From Baseline to Day 43 in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form (8a) T-Score: Estimand 1	PROMIS-SD Short Form 8a is a static 8-item questionnaire, assessed self-perceptions of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items), worrying about sleep (1 item). Each question has five response options ranging in value from 1 to 5. Direction of responses was not same, sometimes "not at all" represents more sleep disturbance; sometimes "not at all" indicates less sleep disturbance. Total raw score for short form with all questions answered was sum of values of response to each question, total score ranged 8 to 40. Lower scores indicate less sleep disturbance. Total raw score converted into T-score. T-score rescaled the raw score into standardized score with mean: 50; standard deviation: 10. Negative changes in scores indicates improvement. Higher values represent more severe sleep disturbance.	Baseline (Day 1), Day 43
DB Treatment Phase: Change From Baseline to Day 43 in the MADRS-6 Total Score: Estimand 1	The 6-item MADRS was a clinician-administered scale designed to measure the core symptoms of depression severity and detected changes due to antidepressant intervention. It is a subset of MADRS (10-item). The MADRS-6 subscale score was the sum of scores for the following MADRS items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Each item is scored from 0 (item not present or normal) to 6 (most severe or continuous presence of symptoms); the overall score ranges from 0 to 36, higher scores represented a more severe condition. Negative change in score indicates improvement.	Baseline (Day 1), Day 43
DB Treatment Phase: Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS at Day 43	Percentage of participants with response on depressive symptoms scale based on MADRS total score at Day 43 were reported. Responders were defined as participants with a >=50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. The MADRS is a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant intervention. Scale has 10 items(apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts) each of which was scored from 0 (not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is sum of scores from individual question items, which ranged from 0 to 60. Higher scores indicates more severe condition. Negative changes in MADRS total score indicates improvement.	At Day 43
DB Treatment Phase: Change From Baseline to Day 43 in Patient Health Questionnaire 9-item (PHQ-9) Total Score	The PHQ-9 was 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) MDD criteria. Each item was rated on a 4 points scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses were summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in PHQ-9 total score indicated improvement.	Baseline (Day 1), Day 43
OL Treatment Phase: Change From Baseline Over Time in MADRS Total Score	MADRS was a clinician-administered scale designed to measure depression severity and detected 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). MADRS total score was sum of scores from individual question items, which ranged from 0-60. Higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.	OL Baseline (Day 1 [Day 43 from study baseline]), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
OL Treatment Phase: Change From Baseline Over Time in the Clinical Global Impression-Severity (CGI-S) Score	The CGI-S (depression) provided an overall clinician-determined summary measure of severity of the participant's illness that considers all available information, included knowledge of participant's history, psychosocial circumstances, symptoms, behavior, impact of symptoms on participant's ability to function. CGI-S evaluated severity of psychopathology on a scale of 1 to 7. The CGI-S was 7-point global assessment scale that measures clinician's impression of severity of illness, rating: 1=normal (not at all ill), 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill participants, with higher scores indicate worsening. Negative changes in CGI-S score indicate improvement.	OL Baseline (Day 1 [Day 43 from study baseline]), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
OL Treatment Phase: Change From Baseline Over Time in the MADRS-WOSI Total Score	The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. MADRS-WOSI was defined as the full MADRS without the sleep item. The MADRS-WOSI scale consisted of 9 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS-WOSI total score was the sum of scores from individual question items, which ranged from 0 to 54, higher scores represented a more severe condition. The MADRS-WOSI evaluated apparent sadness, reported sadness, inner tension, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Negative change in MADRS total score indicated improvement.	OL Baseline (OL Day 1 [Day 43 from study baseline]), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
OL Treatment Phase: Change From Baseline Over Time in Sleep Disturbance Using the PROMIS-SD Short Form 8a T-Score	PROMIS-SD Short Form 8a is a static 8-item questionnaire, assessed self-perceptions of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items), worrying about sleep (1 item). Each question has five response options ranging in value from one to five. Direction of responses was not same, sometimes "not at all" represents more sleep disturbance; sometimes "not at all" indicates less sleep disturbance. Total raw score for short form with all questions answered was sum of values of response to each question, total score ranged 8 to 40. Lower scores indicate less sleep disturbance. Total raw score converted into T-score. T-score rescaled the raw score into standardized score with mean:50; standard deviation:10. Negative changes in scores indicates improvement. Higher values represent more severe sleep disturbance.	OL Baseline (OL Day 1 [Day 43 from study baseline]), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Actual): April 25, 2023
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 28, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; seltorexant
• Other Study ID Numbers: CR108804; 2020-000337-40 (EudraCT Number); 42847922MDD3001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No