A Study of Aticaprant as Adjunctive Therapy in Adult Participants With Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy
- Conditions
- Depressive Disorder, MajorAnhedonia
- Interventions
- Drug: AticaprantOther: Placebo
- Registration Number
- NCT05455684
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy of aticaprant compared with placebo as adjunctive therapy to an antidepressant in improving depressive symptoms in adult participants with major depressive disorder (MDD) with moderate-to-severe anhedonia (ANH+) 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
Depression is a common and serious psychiatric disorder which is a leading cause of disability worldwide and is associated with elevated mortality and suicide risk. Aticaprant (JNJ-67953964) is a once daily, highly selective kappa opioid receptor (KOR) antagonist, with demonstrated selectivity over mu opioid receptor (MOR) and delta opioid receptor (DOR) being developed for adjunctive treatment of major depressive disorder (MDD) with moderate-to-severe anhedonia (ANH+). The study consists of a screening phase (up to 30 days prior to randomization), double-blind treatment phase (43 days), and follow-up phase (up to 14 days). The total duration of the study will be up to 87 days. Safety evaluations including adverse events, physical examinations, urine drug test, alcohol breath tests, and clinical laboratory tests will be assessed at specific time points during this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 513
- Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and baseline
- Have a Hamilton Depression Rating Scale 17 item (HDRS-17) total score of 20 or higher at the first and second screening interviews and must not demonstrate a clinically significant improvement between the first and the second independent HDRS-17 assessments
- Meet Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) diagnostic criteria for recurrent or single episode 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). Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age
- Have had an inadequate response to at least 1 oral antidepressant treatment, administered at an adequate dose (at or above the minimum therapeutic dose per Massachusetts General Hospital Antidepressant Treatment Response Questionnaire [MGH ATRQ]) and duration (at least 6 weeks) in the current episode of depression. An inadequate response is defined as less than(<) 50% reduction in depressive symptom severity but with some improvement (>0%) (ie, there may be minimal to moderate symptomatic improvement since the initiation of treatment, but some of the initial symptoms are still present, troubling to the participant and affecting behavior and function), as assessed by the MGH ATRQ
- Is currently 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 approved formulation and available in the participating country/territory: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine at a stable dose for at least 6 weeks. The current antidepressant cannot be the first antidepressant treatment for the first lifetime episode of depression
- Participant's current major depressive episode, and antidepressant treatment response in the current depressive episode, must all be confirmed by the site independent qualification assessment
- Have had in the current depressive episode, no response (treatment failure) to 5 or more antidepressant treatments including the current SSRI/SNRI (that is, the one presumed to be continued in the treatment phase) assessed using the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ)
- Has a history or evidence of clinically meaningful noncompliance with current antidepressant therapy
- Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening
- Has had in the current episode an inadequate response to adequate course of intravenous or intranasal ketamine or esketamine, electroconvulsive therapy, vagal nerve stimulation, or deep brain stimulation device
- Has current, or a history (past 6 months), of seizures
- Has a current homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 3 months prior to the start of the Screening Phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS), corresponding to a response of "Yes" on Item 4 or Item 5, or a history of suicidal behavior within the past 6 months prior to the start of the Screening Phase. Participants reporting suicidal ideation with intent to act or suicidal behavior at baseline should be excluded
- Has one or more of the following diagnoses: a) A DSM-5 diagnosis (which has been the primary focus of psychiatric treatment within the past 2 years) of any of the following: panic disorder, generalized anxiety disorder, social anxiety disorder, specific phobia; b) A current (in the past year) DSM-5 diagnosis of: obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), anorexia nervosa, bulimia nervosa; c) A current or prior (lifetime) DSM-5 diagnosis of: a psychotic disorder or MDD with psychotic features, bipolar or related disorders, intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, narcissistic personality disorders, somatoform disorders
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aticaprant Aticaprant Participants will receive aticaprant tablets orally once daily for 42 days during double-blind treatment phase in addition to the current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003). Placebo Placebo Participants will receive matching placebo orally once daily for 42 days during double-blind treatment phase in addition to their current antidepressant (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003).
- Primary Outcome Measures
Name Time Method Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Day 43 Baseline to Day 43 Change from baseline in MADRS total score to Day 43 will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which 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 Percentage of Responders on Depressive Symptoms Scale from Baseline to Day 43 Baseline to Day 43 Percentage of responders on depressive symptoms scale, defined as a greater than or equal to (\>=) 50 percent (%) improvement in MADRS total score from baseline to Day 43 will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which 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.
Change from Baseline in Dimensional Anhedonia Rating Scale (DARS) Total Score to Day 43 Baseline to Day 43 Change from baseline in DARS total score to Day 43 will be reported. DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in major depressive disorder (MDD), and particularly to increase scale generalizability while maintaining specificity. Respondents provide their own examples of rewarding experiences across the domains of hobbies, social activities, food/drink, and sensory experience. Participants answer a set of standardized questions about desire, motivation, effort, and consummatory pleasure with a recall period of "right now" for the examples provided. The instrument is scored as a total sum of all items (range 0-68) with higher scores reflecting increased motivation, effort and pleasure (that is, less anhedonia).
Change from Baseline in DARS Total Score Over Time Baseline up to Day 57 Change from baseline in DARS total score over time will be reported. DARS is a 17-item self-report questionnaire that was designed to assess anhedonia in MDD, and particularly to increase scale generalizability while maintaining specificity. Respondents provide their own examples of rewarding experiences across the domains of hobbies, social activities, food/drink, and sensory experience. Participants answer a set of standardized questions about desire, motivation, effort and consummatory pleasure with a recall period of "right now" for the examples provided. The instrument is scored on 0 (not at all) to 4 (very much) and the total score is calculated as a sum of all items (range 0-68) with higher scores reflecting increased motivation, effort, and pleasure (that is, less anhedonia).
Change from Baseline in MADRS Total Score over Time Baseline up to Day 57 Change from baseline in MADRS total score over time will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which 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.
Change from Baseline in the PHQ-9 Anhedonia-specific Item (PHQ-9, item 1) Over Time Baseline up to Day 57 Change from baseline in the PHQ-9 Anhedonia-specific item (PHQ-9, item 1) over time will be reported. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the diagnostic and statistical manual of mental disorders-5th edition (DSM-5) MDD criteria and it is used both as a screening tool and a measure of response to treatment for depression: 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.
Percentage of Participants with a Score Less than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43 Day 43 Percentage of participants with a score \< 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43 will be reported.
Change from Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Short Form-Ability to Participate in Social Roles and Activities - 8a (PROMIS-APS 8a) Over Time Baseline up to Day 57 The PROMIS-APS 8a includes items selected from the PROMIS item bank to provide an assessment of the current degree of involvement in one's usual social roles, activities, and responsibilities, including work, family, friends, and leisure. The 8-item short form will be used in this study, and responses to every item are in a 5-point ordinal scale ranging from 1 = "Always" to 5 = "Never," with higher scores indicating better social functioning. The total scores of PROMIS-APS 8a are scaled on a T-score metric with a mean of 50 and a standard deviation (SD) of 10.
Percentage of Participants with Remission of Depressive Symptoms Defined as a MADRS Total Score <=10 at Day 43 Day 43 Percentage of participants with remission of depressive symptoms, defined as a MADRS total score less than or equal to (\<=) 10 at Day 43 will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which 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.
Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score to Day 43 Baseline to Day 43 Change from baseline in PHQ-9 total score to Day 43 will be reported. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the diagnostic and statistical manual of mental disorders-5th edition (DSM-5) MDD criteria and it is used both as a screening tool and a measure of response to treatment for depression. 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.
Change from Baseline over Time in the Work Productivity and Activity Impairment (WPAI:D) Baseline up to Day 43 The WPAI:D questionnaire is a validated short instrument that assesses impairment in work and other regular activities over the past 7 days. The WPAI questionnaire assesses 4 separate measures: absenteeism (that is , the proportion of work time missed due to MDD), presenteeism (that is, the degree of impairment while working due to MDD), work productivity loss (ie, overall work impairment due to MDD/absenteeism plus presenteeism), and activity impairment (that is, the degree of impairment of regular, nonwork activity due to MDD). The WPAI outcomes are expressed as impairment percentages, with higher values indicating greater impairment and less productivity, that is, worse outcomes.
Trial Locations
- Locations (120)
Narodni ustav dusevniho zdravi
🇨🇿Klecany, Czechia
Praglandia s r o
🇨🇿Prague 5, Czechia
Clintrial s r o
🇨🇿Praha 10, Czechia
AD71 s.r.o.
🇨🇿Praha 10, Czechia
NeuropsychiatrieHK, s.r.o.
🇨🇿Praha 6, Czechia
Psychiatricka ordinace
🇨🇿Usti nad Labem, Czechia
Obudai Egeszsegugyi Centrum Kft
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Bugat Pal Korhaz
🇭🇺Gyongyos, Hungary
Dr Mathe es Tarsa Bt
🇭🇺Kalocsa, Hungary
PsychoTech Kft
🇭🇺Pecs, Hungary
Tolna Megyei Balassa Janos Korhaz
🇭🇺Szekszárd, Hungary
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
🇮🇹Bergamo, Italy
Azienda Ospedaliero Universitaria Mater Domini
🇮🇹Catanzaro, Italy
AUSL LE di Lecce
🇮🇹Lecce, Italy
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base
🇧🇷Sao Jose do Rio Preto, Brazil
A Shine S R O
🇨🇿Plzen, Czechia
Nyiro Gyula Korhaz
🇭🇺Budapest, Hungary
Centrum Badan Klinicznych PI House sp z o o
🇵🇱Gdansk, Poland
SW Biomedical Research LLC
🇺🇸Tucson, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Advanced Research Center Inc
🇺🇸Anaheim, California, United States
Proscience Research Group
🇺🇸Culver City, California, United States
Behavioral Research Specialists LLC
🇺🇸Glendale, California, United States
Asclepes Research
🇺🇸Long Beach, California, United States
Excell Research Inc
🇺🇸Oceanside, California, United States
Syrentis Clinical Research
🇺🇸Santa Ana, California, United States
Viking Clinical Research Ltd
🇺🇸Temecula, California, United States
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Innovative Research of West Florida, Incorporated
🇺🇸Clearwater, Florida, United States
Vertex Research Group, Inc
🇺🇸Clermont, Florida, United States
Gulfcoast Medical Research Center
🇺🇸Fort Myers, Florida, United States
New Life Medical Research Center, Inc.
🇺🇸Hialeah, Florida, United States
Amedica Research Institute Inc
🇺🇸Hialeah, Florida, United States
Convenient Medical Center
🇺🇸Hialeah, Florida, United States
Galiz Research
🇺🇸Hialeah, Florida, United States
Meridian International Research
🇺🇸Miami Gardens, Florida, United States
University of Miami
🇺🇸Miami Lakes, Florida, United States
Pharmax Research Clinic Inc
🇺🇸Miami, Florida, United States
A Plus Research
🇺🇸Miami, Florida, United States
Medical Research Group of Central Florida
🇺🇸Orange City, Florida, United States
USF, Department of Psychiatry and Behavioral Neurosciences
🇺🇸Tampa, Florida, United States
Research Network America
🇺🇸Berwyn, Illinois, United States
Chicago Research Center
🇺🇸Chicago, Illinois, United States
University of Kansas Medical Center Research Institute
🇺🇸Kansas City, Kansas, United States
Clinical Trials of America
🇺🇸Monroe, Louisiana, United States
ActivMed Practices and Research
🇺🇸Methuen, Massachusetts, United States
Psychiatric Care and Research Center (PCRC)
🇺🇸O'Fallon, Missouri, United States
Montefiore Medical Center PRIME
🇺🇸Bronx, New York, United States
Bioscience Research LLC
🇺🇸Mount Kisco, New York, United States
Fieve Clinical Research Inc
🇺🇸New York, New York, United States
Finger Lakes Clinical Research
🇺🇸Rochester, New York, United States
Patient Priority Clinical Sites LLC
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Midwest Clinical Research Center
🇺🇸Dayton, Ohio, United States
Charak Center for Health and Wellness
🇺🇸Garfield Heights, Ohio, United States
Suburban Research Associates
🇺🇸Media, Pennsylvania, United States
University of Pennsylvania - Perelman School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
West Houston Clinical Research Service
🇺🇸Bellaire, Texas, United States
North Texas Clinical Trials
🇺🇸Fort Worth, Texas, United States
Bay Area Clinical Services
🇺🇸Friendswood, Texas, United States
Clinical Trial Network - Houston
🇺🇸Houston, Texas, United States
Alpine Research Organization
🇺🇸Clinton, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Northwest Clinical Research Center
🇺🇸Bellevue, Washington, United States
CENydET - Centro Neurobiologico y de Stress Traumatico
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Hospital Italiano
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
STAT Research S A
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
CIPREC
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Resolution
🇦🇷Ciudad de Mendoza, Argentina
Fundacion Lennox
🇦🇷Cordoba, Argentina
CENPIA
🇦🇷La Plata, Argentina
Instituto Medico de La Fundacion Estudios Clinicos
🇦🇷Rosario, Argentina
Peninsula Therapeutic & Research Group
🇦🇺Frankston, Australia
Albert Road Clinic
🇦🇺Melbourne, Australia
The Alfred Hospital
🇦🇺Melbourne, Australia
Anima
🇧🇪Alken, Belgium
C.H.U. Brugmann
🇧🇪Bruxelles, Belgium
Pz Duffel
🇧🇪Duffel, Belgium
Vitaz
🇧🇪Sint Niklaas, Belgium
Universidade Federal do Ceara Hospital Universitario Walter Cantidio
🇧🇷Fortaleza, Brazil
Instituto Goiano de Neuropsiquiatria
🇧🇷Goiania, Brazil
NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul
🇧🇷Porto Alegre, Brazil
Ruschel Medicina e Pesquisa Clínica Ltda
🇧🇷Rio de Janeiro, Brazil
BR Trials
🇧🇷Sao Paulo, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos
🇧🇷São Bernardo do Campo, Brazil
CPQuali Pesquisa Clinica LTDA ME
🇧🇷São Paulo, Brazil
Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET
🇧🇬Cherven Bryag, Bulgaria
Ambulatory Group practice for specialized help in psychiary Philipopolis ODD
🇧🇬Plovdiv, Bulgaria
Medical Center Mentalcare OOD
🇧🇬Plovdiv, Bulgaria
Mental Health Center - Rousse
🇧🇬Ruse, Bulgaria
Medical Center St. Naum
🇧🇬Sofia, Bulgaria
Mental Health Center - Veliko Tarnovo EOOD
🇧🇬Veliko Tarnovo, Bulgaria
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
ASST Fatebenefratelli Sacco
🇮🇹Milano, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
🇮🇹Siena, Italy
Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski
🇵🇱Belchatow, Poland
Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk
🇵🇱Bialystok, Poland
Specjalistyczna Indywidualna Praktyka Lekarska
🇵🇱Lodz, Poland
SPZOZ Uniwersytecki Szpi.Klin. nr 4 UM w Lodzi
🇵🇱Lodz, Poland
Osrodek Badan Klinicznych CROMED
🇵🇱Poznan, Poland
Specjalistyczny Gabinet Psychiatryczny Kowalkowski Gerard
🇵🇱Torun, Poland
Hospital de Braga
🇵🇹Braga, Portugal
Hospital CUF Inf. Santo
🇵🇹Lisboa, Portugal
Fund. Champalimaud
🇵🇹Lisboa, Portugal
Institucion Hosp Hestia Palau
🇪🇸Barcelona, Spain
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Hosp Regional Univ de Malaga
🇪🇸Malaga, Spain
Hosp. Univ. Son Espases
🇪🇸Palma de Mallorca, Spain
Hosp. El Bierzo
🇪🇸Ponferrada, Spain
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
Hosp. Alvaro Cunqueiro
🇪🇸Vigo, Spain
Hosp. Psiquiatrico Alava
🇪🇸Vitoria, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Goteborg, Sweden
ProbarE i Lund AB
🇸🇪Lund, Sweden
ProbarE i Stockholm AB
🇸🇪Stockholm, Sweden
Studieenheten Akademiskt Specialistcentrum Stockholm
🇸🇪Stockholm, Sweden