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 Therapy

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

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 a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).

Study Overview

• Status: Terminated
• 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 the adjunctive treatment of 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 3 phases: a screening phase (up to 30 days), a double-blind (DB) treatment phase (43 days), and a post treatment follow-up phase (7 to 14 days after DB treatment phase). Total duration of study is up to 12 weeks. Efficacy, safety, pharmacokinetics, and biomarkers will be assessed at specified time points during this study.

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Banfield, Argentina, B1828CKR
    • Clínica Privada Banfield S.A
  • Ciudad Autonoma de Buenos Aires, Argentina, C10154ABQ
    • NOVAIN Neurociencias Group
  • Ciudad Autonoma de Buenos Aires, Argentina, C1425AHQ
    • Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
  • Ciudad Autonoma de Buenos Aires, Argentina, C1013AAB
    • STAT Research S A
  • Cordoba, Argentina, X5003DCE
    • Instituto Médico DAMIC
  • Cordoba, Argentina, X5009BIN
    • Sanatorio Prof. Leon S. Morra
  • Cordoba, Argentina, 5000FJF
    • CEN Consultorios Especializados en Neurociencias
  • La Plata, Argentina, 1900
    • INSA Instituto de Neurociencias San Agustín
  • Rosario, Argentina, 2000
    • C I A P Centro de investigacion y Asistencia en Psiquiatria
  • San Miguel de Tucuman, Argentina, T4000IHE
    • Clinica Mayo de UMCB
• Chile
  • Antofagasta, Chile, 1270244
    • Psicomed Estudios Medicos
  • Santiago, Chile, 7500710
    • Biomedica Research Group
  • Santiago, Chile, 8320000
    • CeCim - Centro de Estudios Clinicos e Investigacion Medica
  • Temuco, Chile, 47811-51
    • Hospital Dr Hernán Henríquez Aravena
• Denmark
  • Hillerod, Denmark, 3400
    • Psykiatrisk Center Nordsjaelland
  • Ålborg, Denmark, 9000
    • Ålborg Universitetshospital
• Finland
  • Helsinki, Finland, 150
    • Eira Hospital
  • Helsinki, Finland, 270
    • Mederon LTD at ARTES
  • Kuopio, Finland, 70110
    • Savon Psykiatripalvelu
  • Oulu, Finland, 90100
    • Oulu Mentalcare Oy
  • Rauma, Finland, 26100
    • Satakunnan Psykiatripalvelu
• Korea, Republic of
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06973
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 1830
    • Eulji General Hospital
• Malaysia
  • Bandar Sunway, Malaysia, 47500
    • Sunway Medical Centre
  • Jalan Pahang, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Sibu, Malaysia, 96001
    • Hospital Sibu
• Poland
  • Bialystok, Poland, 15-756
    • Podlaskie Centrum Psychogeriatrii
  • Czestochowa, Poland, 42-202
    • Synexus Polska Sp. z o.o. Oddzial w Czestochowie
  • Katowice, Poland, 40 040
    • Synexus Polska Sp z o o Oddzial w Katowicach
  • Leszno, Poland, 64-100
    • Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
  • Lodz, Poland, 90 127
    • Synexus Polska Sp z o o
  • Lublin, Poland, 20 109
    • Centrum Medyczne Luxmed Sp z o o
• Slovakia
  • Bratislava, Slovakia, 82007
    • Psychiatricka Ambulancia Mentum S.R.O.
  • Svidník, Slovakia, 089 01
    • Psychiatricka Ambulancia Centrum Zdravia R.B.K. S.R.O.
  • Vranov nad Toplou, Slovakia, 9301
    • Crystal Comfort s.r.o.
  • Zlate Moravce, Slovakia, 95301
    • BONA MEDIC, s.r.o.
• Ukraine
  • Kharkiv, Ukraine, 61068
    • Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'
  • Kherson, Ukraine, 73488
    • CNPE'Kherson Regional Institution of Mental Care'of Kherson Regional Council
  • Kyiv, Ukraine, 02192
    • Cnce 'Kyiv City Psychoneurological Hospital #2' of Executive Body of Kyiv City Council (Kcsa)
  • Kyiv, Ukraine, 1133
    • Main Military Clinical Hospital of MDU
  • Kyiv, Ukraine, 3049
    • Kyiv Clinical Railway Hospital #2 of the Branch Health Care Center of the PJSC Ukrainian Railway
  • Lviv, Ukraine, 79021
    • CNCE of the Lviv Regional Council 'Lviv Regional Clinical Psychiatric Hospital'
  • Odesa, Ukraine, 65014
    • CI Odesa Regional Medical Center of Mental Health
  • Oleksandrivka, Ukraine, 67513
    • CNCE Odesa regional psychiatric hospital #2 Odesa regional council
  • Poltava, Ukraine, 36006
    • Poltava O.F. Maltsev RC Psychiatric Hospital Dept #9 (Ad-P Dept) HSEIU Ukrainian MSA
  • Smila, Ukraine, 20708
    • CNCE 'Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council'
  • Vinnytsia, Ukraine, 21005
    • CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Altea Research Institute
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners
  • California
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists LLC
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Long Beach, California, United States, 90807
      • Alliance for Research
    • Oceanside, California, United States, 92056
      • Excell Research Inc
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc.
  • Florida
    • Miami, Florida, United States, 33133
      • Innova Clinical Trials
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic Inc
    • North Miami Beach, Florida, United States, 33162
      • Harmony Clinical Research Inc
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Orlando, Florida, United States, 32806
      • Synexus Research Orlando
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
    • The Villages, Florida, United States, 32162
      • Compass Research LLC-Bioclinica Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus Clinical Research US Inc
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute, LLC
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Phoenix Medical Research, Inc.
  • Michigan
    • Ann Arbor, Michigan, United States, 48108
      • Michigan Clinical Research Institute
  • New York
    • New York, New York, United States, 10128
      • Eastside Comprehensive Medical Services
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Community Research Management Associates, Inc.
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites LLC
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Intend Research
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company
  • Texas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research LLC
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research, LLC

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 duration 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 other than insomnia present, and overall good tolerability, as assessed by the 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
• 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 [ie], 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 of the 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 clinical laboratory tests performed at screening
• Participant must be medically stable on the basis of the following: 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, severe renal insufficiency (creatinine clearance [CrCl] < 30 milliliter per minute [mL/min]); clinically significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders and uncontrolled Type 1 or Type 2 diabetes mellitus
• Has clinically significant hepatic disease as defined by >=2*Upper Limit of Normal (ULN) increase of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening
• 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 massachusetts general hospital-antidepressant treatment response questionnaire [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 orally once daily from Day 1 to Day 42 (until the end of Week 6).	Drug: Seltorexant; Participants will receive Seltorexant tablets.
Placebo Comparator: Placebo; Participants will receive matching placebo tablets orally once daily from Day 1 to Day 42 (until the end of Week 6).	Drug: Placebo; Participants will receive matching placebo tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 43 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	The MADRS was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. The scale consisted of 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 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.	Baseline (Day 1), Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 43 in the MADRS Without Sleep Item (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 (apparent sadness, reported sadness, inner tension, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). Higher scores represented a more severe condition. 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. Negative change in MADRS total score indicated improvement.	Baseline (Day 1), Day 43
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	PROMIS-SD Short Form 8a: 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 5 options ranged 1 to 5. The "direction" of responses was not same, sometimes "not at all" =more sleep disturbance; sometimes "not at all" =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=less sleep disturbance. Total raw score converted into T-score. T-score rescaled the raw score into standardized score with mean-50; SD-10. Negative changes in scores=improvement. Higher PROMIS T-score represents more concept measured. Negatively worded (like sleep disturbance), T-score of 60 was one SD worse than average. By comparison, T-score of 40 was one SD better than average. T-score of 50 or above was clinically significant level of sleep disturbance.	Baseline (Day 1), Day 43
Change From Baseline to Day 43 in the 6-item MADRS (MADRS-6) Total Score	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 was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), the overall score ranges from 0 to 36, higher scores represented a more severe condition. Negative changes in MADRS-6 total score indicate improvement.	Baseline (Day 1), Day 43
Percentage of Participants Who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43	Percentage of participants who achieved 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 was a clinician-rated scale designed to measure depression severity and detected changes due to antidepressant treatment. The scale consisted of 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 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. Negative change in MADRS total score indicated improvement.	At Day 43
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) major depressive disorder (MDD) criteria. Each item was 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 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 was 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

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 15, 2020
• Primary Completion (Actual): May 24, 2022
• Study Completion (Actual): July 14, 2022

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: CR108805; 42847922MDD3002 (Other Identifier: Janssen Research & Development, LLC); 2020-000338-16 (EudraCT Number)

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 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

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