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

Depressive Disorder, Major Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04532749
• Other study ID #: CR108805
• Secondary ID: 42847922MDD30022
• Status: Terminated
• Phase: Phase 3
• Start date: September 15, 2020
• Est. completion date: July 14, 2022

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 212
• Est. completion date: July 14, 2022
• Est. primary completion date: May 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Seltorexant
Participants will receive Seltorexant tablets.
• Placebo
Participants will receive matching placebo tablets.

Locations

Country	Name	City	State
Argentina	Clínica Privada Banfield S.A	Banfield
Argentina	Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales	Ciudad Autonoma de Buenos Aires
Argentina	NOVAIN Neurociencias Group	Ciudad Autonoma de Buenos Aires
Argentina	STAT Research S.A.	Ciudad Autonoma de Buenos Aires
Argentina	CEN Consultorios Especializados en Neurociencias	Cordoba
Argentina	Instituto Medico DAMIC	Cordoba
Argentina	Sanatorio Prof. Leon S. Morra	Cordoba
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 Tucuman
Chile	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
Denmark	Ålborg Universitetshospital	Ålborg
Denmark	Psykiatrisk Center Nordsjaelland	Hillerod
Finland	Eira Hospital	Helsinki
Finland	Mederon LTD at ARTES	Helsinki
Finland	Savon Psykiatripalvelu	Kuopio
Finland	Oulu Mentalcare Oy	Oulu
Finland	Satakunnan Psykiatripalvelu	Rauma
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Korea University Ansan Hospital	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Chung-Ang University Hospital	Seoul
Korea, Republic of	Eulji General Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	Sunway Medical Centre	Bandar Sunway
Malaysia	Hospital Kuala Lumpur	Jalan Pahang
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Sibu	Sibu
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok
Poland	Synexus Polska Sp. z o.o. Oddzial w Czestochowie	Czestochowa
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
Slovakia	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 Toplou
Slovakia	BONA MEDIC, s.r.o.	Zlate Moravce
Ukraine	Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'	Kharkiv
Ukraine	CNPE'Kherson Regional Institution of Mental Care'of Kherson Regional Council	Kherson,Vil. Stepanivka
Ukraine	Cnce 'Kyiv City Psychoneurological Hospital #2' of Executive Body of Kyiv City Council (Kcsa)	Kyiv
Ukraine	Kyiv Clinical Railway Hospital #2 of the Branch Health Care Center of the PJSC Ukrainian Railway	Kyiv
Ukraine	Main Military Clinical Hospital of MDU	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
United States	Michigan Clinical Research Institute	Ann Arbor	Michigan
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	Community Research Management Associates, Inc.	Cincinnati	Ohio
United States	Patient Priority Clinical Sites LLC	Cincinnati	Ohio
United States	InSite Clinical Research LLC	DeSoto	Texas
United States	Behavioral Research Specialists LLC	Glendale	California
United States	Sun Valley Research Center	Imperial	California
United States	Preferred Research Partners	Little Rock	Arkansas
United States	Alliance for Research	Long Beach	California
United States	Innova Clinical Trials	Miami	Florida
United States	Pharmax Research Clinic Inc	Miami	Florida
United States	Eastside Comprehensive Medical Services	New York	New York
United States	Intend Research	Norman	Oklahoma
United States	Harmony Clinical Research Inc	North Miami Beach	Florida
United States	Excell Research Inc	Oceanside	California
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	Synexus Research Orlando	Orlando	Florida
United States	Altea Research Institute	Phoenix	Arizona
United States	Phoenix Medical Research, Inc.	Prairie Village	Kansas
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California
United States	Stedman Clinical Trials	Tampa	Florida
United States	Compass Research LLC-Bioclinica Research	The Villages	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Denmark,  Finland,  Korea, Republic of,  Malaysia,  Poland,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Day 43	MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.	Baseline to Day 43
Secondary	Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score to Day 43	MADRS-WOSI considered 9 of the 10 MADRS items, excluding "reduced sleep" item. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity.	Baseline to Day 43
Secondary	Change from Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a T-score to Day 43	The PROMIS-Sleep Disturbance (PROMIS-SD) is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The full PROMIS-SD includes 27 items with each item based on a 7-day recall period and assessed on a 5 level Likert-type scale. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. A higher score on 5 of the 8 items reflects a worse outcome, whereas a higher score on 3 items reflects an improved outcome; therefore, the directionality of the 8 item scores are first synchronized prior to calculation of the total raw score. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 8-item form, the lowest possible raw score is 8; the highest possible raw score is 40. Higher overall score indicates more sleep disturbance.	Baseline to Day 43
Secondary	Change from Baseline in the MADRS-6 Total Score to Day 43	The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).	Baseline to Day 43
Secondary	Percentage of Participants with Response on Depressive Symptoms Scale Based on Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Day 43	Responders are defined as participants with greater than or equal to (>=) 50 percent (%) improvement in the MADRS total score from baseline to Day 43.	Baseline to Day 43
Secondary	Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score to Day 43	The PHQ-9 is 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 is 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 are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.	Baseline to Day 43