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
- Registration Number
- NCT04532749
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 212
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Seltorexant Seltorexant Participants will receive Seltorexant orally once daily from Day 1 to Day 42 (until the end of Week 6). Placebo Placebo Participants will receive matching placebo tablets orally once daily from Day 1 to Day 42 (until the end of Week 6).
- Primary Outcome Measures
Name Time Method Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Day 43 Baseline 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.
- Secondary Outcome Measures
Name Time Method Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score to Day 43 Baseline 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.
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 Baseline 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.
Change from Baseline in the MADRS-6 Total Score to Day 43 Baseline 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).
Percentage of Participants with Response on Depressive Symptoms Scale Based on Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Day 43 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.
Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score to Day 43 Baseline 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.
Trial Locations
- Locations (80)
Synexus Polska Sp z o o Oddzial w Katowicach
🇵🇱Katowice, Poland
Synexus Polska Sp z o o
🇵🇱Lodz, Poland
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
ClÃnica Privada Banfield S.A
🇦🇷Banfield, Argentina
STAT Research S A
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
NOVAIN Neurociencias Group
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
🇦🇷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 AgustÃn
🇦🇷La Plata, Argentina
C I A P Centro de investigacion y Asistencia en Psiquiatria
🇦🇷Rosario, Argentina
Clinica Mayo de UMCB
🇦🇷San Miguel de Tucuman, 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
Psykiatrisk Center Nordsjaelland
🇩🇰Hillerod, Denmark
Ã…lborg Universitetshospital
🇩🇰Ålborg, Denmark
Eira Hospital
🇫🇮Helsinki, Finland
Mederon LTD at ARTES
🇫🇮Helsinki, Finland
Savon Psykiatripalvelu
🇫🇮Kuopio, Finland
Oulu Mentalcare Oy
🇫🇮Oulu, Finland
Satakunnan Psykiatripalvelu
🇫🇮Rauma, Finland
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Korea University Ansan Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Chung-Ang University Hospital
🇰🇷Seoul, Korea, Republic of
Eulji General Hospital
🇰🇷Seoul, Korea, Republic of
Sunway Medical Centre
🇲🇾Bandar Sunway, Malaysia
Hospital Kuala Lumpur
🇲🇾Jalan Pahang, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Hospital Sibu
🇲🇾Sibu, Malaysia
Podlaskie Centrum Psychogeriatrii
🇵🇱Bialystok, Poland
Synexus Polska Sp. z o.o. Oddzial w Czestochowie
🇵🇱Czestochowa, Poland
Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
🇵🇱Leszno, 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.
🇸🇰SvidnÃk, Slovakia
Crystal Comfort s.r.o.
🇸🇰Vranov nad Toplou, Slovakia
BONA MEDIC, s.r.o.
🇸🇰Zlate Moravce, Slovakia
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