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

NCT ID: NCT04532749

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2022-07-14

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).

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.

Conditions

Depressive Disorder, Major

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Seltorexant

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

Group Type: EXPERIMENTAL

Seltorexant

Intervention Type: DRUG

Participants will receive Seltorexant tablets.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo tablets.

Interventions

Seltorexant

Participants will receive Seltorexant tablets.

Intervention Type: DRUG

Placebo

Participants will receive matching placebo tablets.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Altea Research Institute

Phoenix, Arizona, United States

Preferred Research Partners

Little Rock, Arkansas, United States

Behavioral Research Specialists LLC

Glendale, California, United States

Sun Valley Research Center

Imperial, California, United States

Alliance for Research

Long Beach, California, United States

Excell Research Inc

Oceanside, California, United States

California Neuroscience Research Medical Group, Inc.

Sherman Oaks, California, United States

Pharmax Research Clinic Inc

Miami, Florida, United States

Innova Clinical Trials

Miami, Florida, United States

Harmony Clinical Research Inc

North Miami Beach, Florida, United States

Medical Research Group of Central Florida

Orange City, Florida, United States

Synexus Research Orlando

Orlando, Florida, United States

Stedman Clinical Trials

Tampa, Florida, United States

Compass Research LLC-Bioclinica Research

The Villages, Florida, United States

Synexus Clinical Research US Inc

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Uptown Research Institute, LLC

Chicago, Illinois, United States

Phoenix Medical Research, Inc.

Prairie Village, Kansas, United States

Michigan Clinical Research Institute

Ann Arbor, Michigan, United States

Eastside Comprehensive Medical Services

New York, New York, United States

Community Research Management Associates, Inc.

Cincinnati, Ohio, United States

Patient Priority Clinical Sites LLC

Cincinnati, Ohio, United States

Intend Research

Norman, Oklahoma, United States

IPS Research Company

Oklahoma City, Oklahoma, United States

InSite Clinical Research LLC

DeSoto, Texas, United States

Pillar Clinical Research, LLC

Richardson, Texas, United States

Clínica Privada Banfield S.A

Banfield, , Argentina

STAT Research S A

Buenos Aires, , Argentina

NOVAIN Neurociencias Group

Buenos Aires, , Argentina

Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales

Buenos Aires, , Argentina

CEN Consultorios Especializados en Neurociencias

Córdoba, , Argentina

Instituto Medico DAMIC

Córdoba, , Argentina

Sanatorio Prof. Leon S. Morra

Córdoba, , Argentina

INSA Instituto de Neurociencias San Agustín

La Plata, , Argentina

C I A P Centro de investigacion y Asistencia en Psiquiatria

Rosario, , Argentina

Clinica Mayo de UMCB

San Miguel de Tucumán, , Argentina

Psicomed Estudios Medicos

Antofagasta, , Chile

BioMedica Research Group

Santiago, , Chile

CeCim - Centro de Estudios Clinicos e Investigacion Medica

Santiago, , Chile

Hospital Dr Hernan Henriquez Aravena

Temuco, , Chile

Ålborg Universitetshospital

Aalborg, , Denmark

Psykiatrisk Center Nordsjaelland

Hillerød, , Denmark

Eira Hospital

Helsinki, , Finland

Mederon LTD at ARTES

Helsinki, , Finland

Savon Psykiatripalvelu

Kuopio, , Finland

Oulu Mentalcare Oy

Oulu, , Finland

Satakunnan Psykiatripalvelu

Rauma, , Finland

Hospital Kuala Lumpur

Jalan Pahang, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Hospital Sibu

Sibu, , Malaysia

Sunway Medical Centre

Sunway City, , Malaysia

Podlaskie Centrum Psychogeriatrii

Bialystok, , Poland

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

Częstochowa, , Poland

Synexus Polska Sp z o o Oddzial w Katowicach

Katowice, , Poland

Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS

Leszno, , Poland

Synexus Polska Sp z o o

Lodz, , Poland

Centrum Medyczne Luxmed Sp z o o

Lublin, , Poland

Psychiatricka Ambulancia Mentum S.R.O.

Bratislava, , Slovakia

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

Svidník, , Slovakia

Crystal Comfort s.r.o.

Vranov nad Topľou, , Slovakia

BONA MEDIC, s.r.o.

Zlaté Moravce, , Slovakia

Chonnam National University Hospital

Gwangju, , South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Korea University Ansan Hospital

Gyeonggi-do, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Chung-Ang University Hospital

Seoul, , South Korea

Eulji General Hospital

Seoul, , South Korea

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

Kharkiv, , Ukraine

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

Kherson, , Ukraine

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

Kyiv, , Ukraine

Main Military Clinical Hospital of MDU

Kyiv, , Ukraine

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

Kyiv, , Ukraine

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

Lviv, , Ukraine

CI Odesa Regional Medical Center of Mental Health

Odesa, , Ukraine

CNCE Odesa regional psychiatric hospital #2 Odesa regional council

Oleksandrivka, , Ukraine

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

Poltava, , Ukraine

CNCE 'Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council'

Smila, , Ukraine

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

Vinnytsia, , Ukraine

Countries

United States; Argentina; Chile; Denmark; Finland; Malaysia; Poland; Slovakia; South Korea; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

42847922MDD3002

Identifier Type: OTHER

Identifier Source: secondary_id

2020-000338-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108805

Identifier Type: -

Identifier Source: org_study_id