Clinical trial NCT04533529: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-08-31
Enrollment: 588
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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.

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 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

Primary outcomes:
measure: Double-blind (DB) Treatment Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline, Day 43
measure: Open-Label (OL) Treatment Phase: Number of Participants with Adverse Events (AEs) including AEs of Special Interest (AESI) as a Measure of Safety and Tolerability
timeFrame: 1 year
measure: OL Treatment Phase: Change From Baseline in Blood Pressure
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change From Baseline in Pulse Rate
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change From Baseline in Weight
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change From Baseline in Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Physician Withdrawal Checklist (PWC-20) Scores
timeFrame: End of Treatment/Early withdrawal to end of the Follow-up visit (up to 14 days)
measure: OL Treatment Phase: Number of Participants with Laboratory Abnormalities
timeFrame: Up to 1 year
measure: OL Treatment Phase: Change From Baseline in QTc Interval
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change from Baseline in Heart Rate (HR)
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change from Baseline in QRS Interval
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change from Baseline in PR Interval
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change From Baseline in QT Interval
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Participant-reported Sexual Functioning Using Arizona Sexual Experiences Scale (ASEX) Score
timeFrame: Up to 1 year
Secondary outcomes:
measure: DB Treatment Phase: Change From Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score
timeFrame: Baseline and Day 43
measure: DB Treatment Phase: Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a T-score
timeFrame: Baseline and Day 43
measure: DB Treatment Phase: Change From Baseline in the MADRS-6 Total Score
timeFrame: Baseline and Day 43
measure: DB Treatment Phase: Percentage of Participants with Response on Depressive Symptoms Scale Based on Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Day 43
measure: DB Treatment Phase: Change From Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score
timeFrame: Baseline and Day 43
measure: DB Treatment Phase: Number of Participants with Adverse Events (AEs) including AEs of Special Interest (AESI) as a Measure of Safety and Tolerability
timeFrame: Up to Day 50 to 57 (every two weeks)
measure: OL Treatment Phase: Change From Baseline Over Time in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change From Baseline Over Time in the Clinical Global Impression-Severity (CGI S) Score
timeFrame: Baseline (Day 43), up to 1 year
measure: OL Treatment Phase: Change from Baseline Over Time in the MADRS-WOSI Total Score
timeFrame: Baseline (of OL phase), up to 1 year
measure: OL Treatment Phase: Change From Baseline Over Time in Sleep Disturbance Using the PROMIS SD Short Form 8a T-score
timeFrame: Baseline (Day 43), up to Year 1
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Research Center Inc
state: California
city: Cerritos
country: United States
facility: Synexus
state: California
city: Irvine
country: United States
facility: Irvine Clinical Research
state: California
city: La Habra
country: United States
facility: Omega Clinical Trials LLC
state: California
city: Lemon Grove
country: United States
facility: Synergy East
state: California
city: Los Angeles
country: United States
facility: Semel Institute for Neuroscience and Human Behavior
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Oakland
country: United States
facility: Pacific Research Partners
state: California
city: Oceanside
country: United States
facility: North County Clinical Research
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Temecula
country: United States
facility: Viking Pharmaceutical Trials Inc. dba Viking Clinical Research
state: California
city: Cromwell
country: United States
facility: Connecticut Clinical Trials LLC
state: Connecticut
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical NeuroScience Solutions Inc
state: Florida
city: Miami Springs
country: United States
facility: Galiz Research
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic Inc
state: Florida
city: Miami
country: United States
facility: Medical Research Center of Miami II Inc
state: Florida
city: Miami
country: United States
facility: Phoenix Medical Research, Inc.
state: Florida
city: North Bay Village
country: United States
facility: Bravo Health Care Center
state: Florida
city: Orlando
country: United States
facility: APG Research LLC
state: Florida
city: Orlando
country: United States
facility: Combined Research Orlando
state: Florida
city: Orlando
country: United States
facility: Nova Psychiatry INC
state: Florida
city: Elgin
country: United States
facility: Revive Research Institute
state: Illinois
city: Joliet
country: United States
facility: Joliet Center for Clinical Research
state: Illinois
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Oak Brook
country: United States
facility: American Medical Research, Inc.
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Shreveport
country: United States
facility: Louisiana Clinical Research
state: Louisiana
city: Watertown
country: United States
facility: Adams Clinical
state: Massachusetts
city: Bloomfield Hills
country: United States
facility: Neurobehavioral Medicine Group
state: Michigan
city: Saint Charles
country: United States
facility: Midwest Research Group - St. Charles Psychiatric Associates
state: Missouri
city: Saint Louis
country: United States
facility: Mid-America Clinical Research, LLC
state: Missouri
city: Saint Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Research Institute, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute, LLC.
state: New Jersey
city: Jamaica
country: United States
facility: Synexus Clinical Research US Inc
state: New York
city: Mount Kisco
country: United States
facility: Bioscience Research LLC
state: New York
city: Avon Lake
country: United States
facility: Haidar Almhana Nieding
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Mason
country: United States
facility: Lindner Center of Hope
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman School of Medicine
state: Pennsylvania
city: Dallas
country: United States
facility: Relaro Medical Trials
state: Texas
city: Fort Worth
country: United States
facility: North Texas Clinical Trials
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates
state: Texas
city: Clinton
country: United States
facility: Alpine Research Organization
state: Utah
city: Rutland
country: United States
facility: Green Mountain Research Institute
state: Vermont
city: Belo Horizonte
country: Brazil
facility: CPN - Centro de Pesquisa em Neurociências Ltda
city: Brasilia
country: Brazil
facility: CCB Centro Cardiologico de Brasilia Ltda - CCB Cardiologia
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba
city: Fortaleza
country: Brazil
facility: Universidade Federal do Ceara Hospital Universitario Walter Cantidio
city: Passo Fundo
country: Brazil
facility: Instituto Mederi de Pesquisa e Saude
city: Rio de Janeiro
country: Brazil
facility: Ruschel Medicina e Pesquisa Clínica Ltda
city: Sao Paulo
country: Brazil
facility: SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto Bairral de Psiquiatria
city: Bourgas
country: Bulgaria
facility: Mental Health Center Prof. Dr. Ivan Temkov
city: Cherven bryag
country: Bulgaria
facility: Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET
city: Kardzhali
country: Bulgaria
facility: State Psychiatric Hospital Kardzhali
city: Plovdiv
country: Bulgaria
facility: Medical center Spectar - Plovdiv EOOD
city: Plovdiv
country: Bulgaria
facility: UMHAT 'Sv. Georgi' EAD
city: Slivnitsa
country: Bulgaria
facility: MHC - Sofia, EOOD
city: Sofia
country: Bulgaria
facility: Medical Center St. Naum
city: Sofia
country: Bulgaria
facility: DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD
city: Sofia
country: Bulgaria
facility: Medical Center Intermedica, OOD
city: Targovishte
country: Bulgaria
facility: Medical center - VAS OOD
city: Vratsa
country: Bulgaria
facility: Mental Health Center - Vratsa EOOD
city: Barranquilla
country: Colombia
facility: Centro de Investigaciones y Proyectos en Neurociencias CIPNA
city: Bello
country: Colombia
facility: HOMO - ESE Hospital Mental de Antioquia
city: Bogota
country: Colombia
facility: Centro de Investigaciones del Sistema Nervioso Grupo Cisne Ltda.
city: Medellin
country: Colombia
facility: Fundacion Centro de Investigacion Clinica CIC
city: Pereira
country: Colombia
facility: Psynapsis Salud Mental S.A.
city: Kladno
country: Czechia
facility: BRAIN-SOULTHERAPY s.r.o.
city: Kutna Hora
country: Czechia
facility: Neuroterapie KH S R O
city: Plzen
country: Czechia
facility: A Shine S R O
city: Praha 10
country: Czechia
facility: Clintrial s r o
city: Praha 6
country: Czechia
facility: Medical Services Prague S R O
city: Monterrey
country: Mexico
facility: Iecsi S.C.
city: Nuevo Leon
country: Mexico
facility: CRI Centro Regiomontano de Investigacion SC
city: San Luis Potosi
country: Mexico
facility: Bind Investigaciones S.C.
city: Saint Petersburg
country: Russian Federation
facility: Psychoneurological dispensary 1
city: Saint-Petersburg
country: Russian Federation
facility: City Psychiatric Hospital of St. Nikolay Chudotvorets
city: St Petersburg
country: Russian Federation
facility: Bekhterev Psychoneurological Research Institute
city: St-Petersburg
country: Russian Federation
facility: Psychoneurological Dispensary of Frunzensky District
city: St. Petersburg
country: Russian Federation
facility: SPb SBIH 'City Psychoneurological Dispensary # 7 (With Inpatient Facilities)'
city: St. Petersburg
country: Russian Federation
facility: St-Petersburg Bekhterev Psychoneurological Research Institute
city: Stavropol
country: Russian Federation
facility: Stavropol Region Psychiatric Hospital #2
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Region Clinical Psychiatric Hospital
city: Bloemfontein
country: South Africa
facility: Farmovs Pty Ltd
city: Bloemfontein
country: South Africa
facility: Iatros International
city: Cape Town
country: South Africa
facility: Cape Town Clinical Research Centre
city: Cape Town
country: South Africa
facility: Flexivest 14 Research
city: Krugersdorp
country: South Africa
facility: DJW Research
city: Mamelodi East
country: South Africa
facility: Stanza Clinical Research Centre : Mamelodi
city: Pretoria
country: South Africa
facility: Synexus Watermeyer
city: Strand
country: South Africa
facility: Somerset West Clinical Research Unit
city: Barcelona
country: Spain
facility: Institucion Hosp Hestia Palau
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Bilbao
country: Spain
facility: Hosp. Univ. de Basurto
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Oviedo
country: Spain
facility: Centro Salud Mental La Corredoria
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Salamanca
country: Spain
facility: Centro de salud San Juan - IBSAL
city: Zamora
country: Spain
facility: Hosp. Prov. de Zamora
city: Halmstad
country: Sweden
facility: Affecta Pskyiatrimottagning
city: Helsingborg
country: Sweden
facility: PharmaSite Helsingborg
city: Lund
country: Sweden
facility: ProbarE i Lund AB
city: Malmo
country: Sweden
facility: PharmaSite
city: Skovde
country: Sweden
facility: Läkarmottagningen
city: Stockholm
country: Sweden
facility: ProbarE i Solna
city: Keelung
country: Taiwan
facility: Chang-Gung Memorial Hospital-Keelung
city: Taipei City
country: Taiwan
facility: Taipei Medical University
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Memorial Hospital- Linkou
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: