Clinical trial NCT04532749: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-08-31
Enrollment: 212
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 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.

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

Primary outcomes:
measure: Change From Baseline to Day 43 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline (Day 1), Day 43
Secondary outcomes:
measure: Change From Baseline to Day 43 in the MADRS Without Sleep Item (MADRS-WOSI) Total Score
timeFrame: Baseline (Day 1), Day 43
measure: 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
timeFrame: Baseline (Day 1), Day 43
measure: Change From Baseline to Day 43 in the 6-item MADRS (MADRS-6) Total Score
timeFrame: Baseline (Day 1), Day 43
measure: Percentage of Participants Who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43
timeFrame: At Day 43
measure: Change From Baseline to Day 43 in Patient Health Questionnaire, 9-item (PHQ-9) Total Score
timeFrame: Baseline (Day 1), Day 43
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Altea Research Institute
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners
state: Arkansas
city: Glendale
country: United States
facility: Behavioral Research Specialists LLC
state: California
city: Imperial
country: United States
facility: Sun Valley Research Center
state: California
city: Long Beach
country: United States
facility: Alliance for Research
state: California
city: Oceanside
country: United States
facility: Excell Research Inc
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: Miami
country: United States
facility: Pharmax Research Clinic Inc
state: Florida
city: Miami
country: United States
facility: Innova Clinical Trials
state: Florida
city: North Miami Beach
country: United States
facility: Harmony Clinical Research Inc
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Orlando
country: United States
facility: Synexus Research Orlando
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: The Villages
country: United States
facility: Compass Research LLC-Bioclinica Research
state: Florida
city: Atlanta
country: United States
facility: Synexus Clinical Research US Inc
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Uptown Research Institute, LLC
state: Illinois
city: Prairie Village
country: United States
facility: Phoenix Medical Research, Inc.
state: Kansas
city: Ann Arbor
country: United States
facility: Michigan Clinical Research Institute
state: Michigan
city: New York
country: United States
facility: Eastside Comprehensive Medical Services
state: New York
city: Cincinnati
country: United States
facility: Community Research Management Associates, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Patient Priority Clinical Sites LLC
state: Ohio
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: DeSoto
country: United States
facility: InSite Clinical Research LLC
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Banfield
country: Argentina
facility: Clínica Privada Banfield S.A
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: STAT Research S A
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: NOVAIN Neurociencias Group
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
city: Cordoba
country: Argentina
facility: CEN Consultorios Especializados en Neurociencias
city: Cordoba
country: Argentina
facility: Instituto Medico DAMIC
city: Cordoba
country: Argentina
facility: Sanatorio Prof. Leon S. Morra
city: La Plata
country: Argentina
facility: INSA Instituto de Neurociencias San Agustín
city: Rosario
country: Argentina
facility: C I A P Centro de investigacion y Asistencia en Psiquiatria
city: San Miguel de Tucuman
country: Argentina
facility: Clinica Mayo de UMCB
city: Antofagasta
country: Chile
facility: Psicomed Estudios Medicos
city: Santiago
country: Chile
facility: BioMedica Research Group
city: Santiago
country: Chile
facility: CeCim - Centro de Estudios Clinicos e Investigacion Medica
city: Temuco
country: Chile
facility: Hospital Dr Hernan Henriquez Aravena
city: Hillerod
country: Denmark
facility: Psykiatrisk Center Nordsjaelland
city: Ålborg
country: Denmark
facility: Ålborg Universitetshospital
city: Helsinki
country: Finland
facility: Eira Hospital
city: Helsinki
country: Finland
facility: Mederon LTD at ARTES
city: Kuopio
country: Finland
facility: Savon Psykiatripalvelu
city: Oulu
country: Finland
facility: Oulu Mentalcare Oy
city: Rauma
country: Finland
facility: Satakunnan Psykiatripalvelu
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Eulji General Hospital
city: Bandar Sunway
country: Malaysia
facility: Sunway Medical Centre
city: Jalan Pahang
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Sibu
country: Malaysia
facility: Hospital Sibu
city: Bialystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Czestochowa
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Czestochowie
city: Katowice
country: Poland
facility: Synexus Polska Sp z o o Oddzial w Katowicach
city: Leszno
country: Poland
facility: Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
city: Lodz
country: Poland
facility: Synexus Polska Sp z o o
city: Lublin
country: Poland
facility: Centrum Medyczne Luxmed Sp z o o
city: Bratislava
country: Slovakia
facility: Psychiatricka Ambulancia Mentum S.R.O.
city: Svidník
country: Slovakia
facility: Psychiatricka Ambulancia Centrum Zdravia R.B.K. S.R.O.
city: Vranov nad Toplou
country: Slovakia
facility: Crystal Comfort s.r.o.
city: Zlate Moravce
country: Slovakia
facility: BONA MEDIC, s.r.o.
city: Kharkiv
country: Ukraine
facility: Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'
city: Kherson
country: Ukraine
facility: CNPE'Kherson Regional Institution of Mental Care'of Kherson Regional Council
city: Kyiv
country: Ukraine
facility: Cnce 'Kyiv City Psychoneurological Hospital #2' of Executive Body of Kyiv City Council (Kcsa)
city: Kyiv
country: Ukraine
facility: Main Military Clinical Hospital of MDU
city: Kyiv
country: Ukraine
facility: Kyiv Clinical Railway Hospital #2 of the Branch Health Care Center of the PJSC Ukrainian Railway
city: Lviv
country: Ukraine
facility: CNCE of the Lviv Regional Council 'Lviv Regional Clinical Psychiatric Hospital'
city: Odesa
country: Ukraine
facility: CI Odesa Regional Medical Center of Mental Health
city: Oleksandrivka
country: Ukraine
facility: CNCE Odesa regional psychiatric hospital #2 Odesa regional council
city: Poltava
country: Ukraine
facility: Poltava O.F. Maltsev RC Psychiatric Hospital Dept #9 (Ad-P Dept) HSEIU Ukrainian MSA
city: Smila
country: Ukraine
facility: CNCE 'Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council'
city: Vinnytsia
country: Ukraine
facility: CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: