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

NCT04532749 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: CR10880542847922MDD30022020-000338-16
• Study Type: interventional
• Target: 212
• Locations: 10 countries
• Sites: 80

Brief Summary

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).

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change From Baseline to Day 43 in the MADRS Without Sleep Item (MADRS-WOSI) Total Score

  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

  Baseline (Day 1), Day 43

• Change From Baseline to Day 43 in the 6-item MADRS (MADRS-6) Total Score

  Baseline (Day 1), Day 43

• Percentage of Participants Who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43

  At Day 43

• Change From Baseline to Day 43 in Patient Health Questionnaire, 9-item (PHQ-9) Total Score

  Baseline (Day 1), Day 43

Study Arms (2)

Seltorexant

EXPERIMENTAL

Participants will receive Seltorexant orally once daily from Day 1 to Day 42 (until the end of Week 6).

Drug: Seltorexant

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo tablets orally once daily from Day 1 to Day 42 (until the end of Week 6).

Drug: Placebo

Interventions

Seltorexant DRUG

Participants will receive Seltorexant tablets.

Seltorexant

Placebo DRUG

Participants will receive matching placebo tablets.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet diagnostic and statistical manual of mental disorders-5th edition (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the structured clinical interview for DSM-5 Axis I disorders-clinical trials version (SCID-CT) diagnosed with first depressive episode prior to age 60. The 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

You may not qualify if:

• Has a recent (last 3 months) history of, or current signs and symptoms of, severe renal insufficiency (creatinine clearance \[CrCl\] \< 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (80)

Altea Research Institute

Phoenix, Arizona, 85012, United States

Location

Preferred Research Partners

Little Rock, Arkansas, 72211, United States

Location

Behavioral Research Specialists LLC

Glendale, California, 91206, United States

Location

Sun Valley Research Center

Imperial, California, 92251, United States

Location

Alliance for Research

Long Beach, California, 90807, United States

Location

Excell Research Inc

Oceanside, California, 92056, United States

Location

California Neuroscience Research Medical Group, Inc.

Sherman Oaks, California, 91403, United States

Location

Pharmax Research Clinic Inc

Miami, Florida, 33126, United States

Location

Innova Clinical Trials

Miami, Florida, 33133, United States

Location

Harmony Clinical Research Inc

North Miami Beach, Florida, 33162, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

Synexus Research Orlando

Orlando, Florida, 32806, United States

Location

Stedman Clinical Trials

Tampa, Florida, 33613, United States

Location

Compass Research LLC-Bioclinica Research

The Villages, Florida, 32162, United States

Location

Synexus Clinical Research US Inc

Atlanta, Georgia, 30328, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Uptown Research Institute, LLC

Chicago, Illinois, 60640, United States

Location

Phoenix Medical Research, Inc.

Prairie Village, Kansas, 66206, United States

Location

Michigan Clinical Research Institute

Ann Arbor, Michigan, 48108, United States

Location

Eastside Comprehensive Medical Services

New York, New York, 10128, United States

Location

Community Research Management Associates, Inc.

Cincinnati, Ohio, 45212, United States

Location

Patient Priority Clinical Sites LLC

Cincinnati, Ohio, 45215, United States

Location

Intend Research

Norman, Oklahoma, 73069, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73106, United States

Location

InSite Clinical Research LLC

DeSoto, Texas, 75115, United States

Location

Pillar Clinical Research, LLC

Richardson, Texas, 75080, United States

Location

Clínica Privada Banfield S.A

Banfield, B1828CKR, Argentina

Location

STAT Research S A

Buenos Aires, C1013AAB, Argentina

Location

NOVAIN Neurociencias Group

Buenos Aires, C10154ABQ, Argentina

Location

Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales

Buenos Aires, C1425AHQ, Argentina

Location

CEN Consultorios Especializados en Neurociencias

Córdoba, 5000FJF, Argentina

Location

Instituto Medico DAMIC

Córdoba, X5003DCE, Argentina

Location

Sanatorio Prof. Leon S. Morra

Córdoba, X5009BIN, Argentina

Location

INSA Instituto de Neurociencias San Agustín

La Plata, 1900, Argentina

Location

C I A P Centro de investigacion y Asistencia en Psiquiatria

Rosario, 2000, Argentina

Location

Clinica Mayo de UMCB

San Miguel de Tucumán, T4000IHE, Argentina

Location

Psicomed Estudios Medicos

Antofagasta, 1270244, Chile

Location

BioMedica Research Group

Santiago, 7500710, Chile

Location

CeCim - Centro de Estudios Clinicos e Investigacion Medica

Santiago, 8320000, Chile

Location

Hospital Dr Hernan Henriquez Aravena

Temuco, 47811-51, Chile

Location

Ålborg Universitetshospital

Aalborg, 9000, Denmark

Location

Psykiatrisk Center Nordsjaelland

Hillerød, 3400, Denmark

Location

Eira Hospital

Helsinki, 150, Finland

Location

Mederon LTD at ARTES

Helsinki, 270, Finland

Location

Savon Psykiatripalvelu

Kuopio, 70110, Finland

Location

Oulu Mentalcare Oy

Oulu, 90100, Finland

Location

Satakunnan Psykiatripalvelu

Rauma, 26100, Finland

Location

Hospital Kuala Lumpur

Jalan Pahang, 50586, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Hospital Sibu

Sibu, 96001, Malaysia

Location

Sunway Medical Centre

Sunway City, 47500, Malaysia

Location

Podlaskie Centrum Psychogeriatrii

Bialystok, 15-756, Poland

Location

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

Częstochowa, 42-202, Poland

Location

Synexus Polska Sp z o o Oddzial w Katowicach

Katowice, 40 040, Poland

Location

Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS

Leszno, 64-100, Poland

Location

Synexus Polska Sp z o o

Lodz, 90 127, Poland

Location

Centrum Medyczne Luxmed Sp z o o

Lublin, 20 109, Poland

Location

Psychiatricka Ambulancia Mentum S.R.O.

Bratislava, 82007, Slovakia

Location

Psychiatricka Ambulancia Centrum Zdravia R.B.K. S.R.O.

Svidník, 089 01, Slovakia

Location

Crystal Comfort s.r.o.

Vranov nad Topľou, 9301, Slovakia

Location

BONA MEDIC, s.r.o.

Zlaté Moravce, 95301, Slovakia

Location

Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Korea University Ansan Hospital

Gyeonggi-do, 15355, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Chung-Ang University Hospital

Seoul, 06973, South Korea

Location

Eulji General Hospital

Seoul, 1830, South Korea

Location

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

Kharkiv, 61068, Ukraine

Location

CNPE'Kherson Regional Institution of Mental Care'of Kherson Regional Council

Kherson, 73488, Ukraine

Location

Cnce 'Kyiv City Psychoneurological Hospital #2' of Executive Body of Kyiv City Council (Kcsa)

Kyiv, 02192, Ukraine

Location

Main Military Clinical Hospital of MDU

Kyiv, 1133, Ukraine

Location

Kyiv Clinical Railway Hospital #2 of the Branch Health Care Center of the PJSC Ukrainian Railway

Kyiv, 3049, Ukraine

Location

CNCE of the Lviv Regional Council 'Lviv Regional Clinical Psychiatric Hospital'

Lviv, 79021, Ukraine

Location

CI Odesa Regional Medical Center of Mental Health

Odesa, 65014, Ukraine

Location

CNCE Odesa regional psychiatric hospital #2 Odesa regional council

Oleksandrivka, 67513, Ukraine

Location

Poltava O.F. Maltsev RC Psychiatric Hospital Dept #9 (Ad-P Dept) HSEIU Ukrainian MSA

Poltava, 36006, Ukraine

Location

CNCE 'Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council'

Smila, 20708, Ukraine

Location

CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU

Vinnytsia, 21005, Ukraine

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

seltorexant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Executive Director CDTL Neuro
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: August 31, 2020
• Study Start: September 15, 2020
• Primary Completion: May 24, 2022
• Study Completion: July 14, 2022
• Last Updated: June 4, 2025
• Results First Posted: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

AR (10); CL (4); DK (2); UA (11); MY (4); FI (5); PL (6); SL (4); KR (8); US (26)