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 (VENTURA-1)

A Randomized, Double-blind, Multicenter, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants With Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy

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).

Study Overview

• Status: Completed
• Conditions: Anhedonia; Depressive Disorder, Major
• Intervention / Treatment: Other: Placebo; Drug: Aticaprant

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.

• Study Type: Interventional
• Enrollment (Actual): 513
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1061AAS
    • CIPREC
  • Buenos Aires, Argentina, 1199
    • Hospital Italiano
  • Buenos Aires, Argentina, C1013AAB
    • STAT Research S A
  • Ciudad Autonoma Buenos Aires, Argentina, 1058 AAJ
    • CENydET - Centro Neurobiologico y de Stress Traumatico
  • Córdoba, Argentina, 5000
    • Fundacion Lennox
  • La Plata, Argentina, 1902
    • CENPIA
  • Mendoza, Argentina, M5502AHV
    • Resolution
  • Rosario, Argentina, S2000DEJ
    • Instituto Medico de la Fundacion Estudios Clinicos
• Australia
  • Frankston, Australia, 3199
    • Peninsula Therapeutic & Research Group
  • Melbourne, Australia, 3004
    • The Alfred Hospital
  • Melbourne, Australia, 3004
    • Albert Road Clinic
• Belgium
  • Alken, Belgium, 3570
    • Anima
  • Brussels, Belgium, 1020
    • C.H.U. Brugmann
  • Duffel, Belgium, 2570
    • Pz Duffel
  • Sint-Niklaas, Belgium, 9100
    • VITAZ
• Brazil
  • Fortaleza, Brazil, 60430-370
    • Universidade Federal do Ceara Hospital Universitario Walter Cantidio
  • Goiânia, Brazil, 74093 040
    • Instituto Goiano de Neuropsiquiatria
  • Porto Alegre, Brazil, 90430001
    • NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul
  • Rio de Janeiro, Brazil, 22270 060
    • Ruschel Medicina e Pesquisa Clínica Ltda
  • São Bernardo do Campo, Brazil, 09715-090
    • CEMEC - Centro Multidisciplinar de Estudos Clínicos
  • São José do Rio Preto, Brazil, 15090-000
    • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base
  • São Paulo, Brazil, 01228-900
    • CPQuali Pesquisa Clinica LTDA ME
  • São Paulo, Brazil, 05003 020
    • BR Trials
• Bulgaria
  • Cherven Bryag, Bulgaria, 5980
    • Ambulatory for Individual Practice for Specialized Medical Care in Psychiatry Dr. Ivo Natsov ET
  • Plovdiv, Bulgaria, 4004
    • Medical Center Mentalcare OOD
  • Plovdiv, Bulgaria, 4002
    • Ambulatory Group practice for specialized help in psychiary Philipopolis ODD
  • Rousse, Bulgaria, 7003
    • Mental Health Center - Rousse
  • Sofia, Bulgaria, 1113
    • Medical Center St. Naum
  • Veliko Tarnovo, Bulgaria, 5000
    • Mental Health Center - Veliko Tarnovo EOOD
• Czechia
  • Klecany, Czechia, 25067
    • Narodni ustav dusevniho zdravi
  • Pilsen, Czechia, 301 00
    • A Shine S R O
  • Prague, Czechia, 109 00
    • AD71 s.r.o.
  • Prague, Czechia, 100 00
    • Clintrial s r o
  • Prague, Czechia, 15000
    • Praglandia s r o
  • Prague, Czechia, 160 00
    • NeuropsychiatrieHK, s.r.o.
  • Ústí nad Labem, Czechia, 400 01
    • Psychiatricka ordinace
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1036
    • Obudai Egeszsegugyi Centrum Kft
  • Budapest, Hungary, 1135
    • Nyiro Gyula Korhaz
  • Gyöngyös, Hungary, 3200
    • Bugat Pal Korhaz
  • Kalocsa, Hungary, 6300
    • Dr Mathe es Tarsa Bt
  • Pécs, Hungary, 7633
    • PsychoTech Kft
  • Szekszárd, Hungary, 7100
    • Tolna Megyei Balassa János Kórház
• Italy
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
  • Catanzaro, Italy, 88100
    • Azienda Ospedaliero Universitaria Mater Domini
  • Lecce, Italy, 73100
    • AUSL LE di Lecce
  • Milan, Italy, 20122
    • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Milan, Italy
    • Ospedale San Raffaele
  • Milan, Italy, 20157
    • ASST Fatebenefratelli Sacco
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
• Poland
  • Bełchatów, Poland, 97-400
    • Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski
  • Bialystok, Poland, 15-404
    • Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk
  • Gdansk, Poland, 80 546
    • Centrum Badan Klinicznych PI House sp z o o
  • Lodz, Poland, 90-009
    • Specjalistyczna Indywidualna Praktyka Lekarska
  • Lodz, Poland, 92-215
    • SPZOZ Uniwersytecki Szpi.Klin. nr 4 UM w Lodzi
  • Poznan, Poland, 61-360
    • Osrodek Badan Klinicznych CROMED
  • Torun, Poland, 87 100
    • Specjalistyczny Gabinet Psychiatryczny Kowalkowski Gerard
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga
  • Lisbon, Portugal, 1350 179
    • Hospital CUF Inf. Santo
  • Lisbon, Portugal, 1400 038
    • Fund. Champalimaud
• Spain
  • Barcelona, Spain, 08025
    • Institucion Hosp Hestia Palau
  • Barcelona, Spain, 08036
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Málaga, Spain, 29011
    • Hosp Regional Univ de Malaga
  • Palma de Mallorca, Spain, 07120
    • Hosp. Univ. Son Espases
  • Ponferrada, Spain, 24404
    • Hosp. El Bierzo
  • Sabadell, Spain, 08208
    • Corporacio Sanitari Parc Tauli
  • Vigo, Spain, 36312
    • Hosp. Alvaro Cunqueiro
  • Vitoria-Gasteiz, Spain, 01006
    • Hosp. Psiquiatrico Alava
• Sweden
  • Gothenburg, Sweden, 416 85
    • Sahlgrenska Universitetssjukhuset
  • Lund, Sweden, 22222
    • ProbarE i Lund AB
  • Stockholm, Sweden, 113 29
    • ProbarE i Stockholm AB
  • Stockholm, Sweden, 113 61
    • Studieenheten Akademiskt Specialistcentrum Stockholm
• United States
  • Arizona
    • Tucson, Arizona, United States, 85713
      • University of Arizona
    • Tucson, Arizona, United States, 85712
      • SW Biomedical Research LLC
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center Inc
    • Culver City, California, United States, 90230
      • ProScience Research Group
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists LLC
    • Long Beach, California, United States, 90807
      • Asclepes Research
    • Oceanside, California, United States, 92056
      • Excell Research Inc
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Temecula, California, United States, 92591
      • Viking Clinical Research Ltd
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Incorporated
    • Clermont, Florida, United States, 34711
      • Vertex Research Group, Inc
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Medical Research Center
    • Hialeah, Florida, United States, 33016
      • Galiz Research
    • Hialeah, Florida, United States, 33012
      • New Life Medical Research Center, Inc.
    • Hialeah, Florida, United States, 33013
      • Amedica Research Institute Inc
    • Hialeah, Florida, United States, 33013
      • Convenient Medical Center
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic Inc
    • Miami, Florida, United States, 33144
      • A Plus Research
    • Miami Gardens, Florida, United States, 33014
      • Meridian International Research
    • Miami Lakes, Florida, United States, 33016
      • University of Miami
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Tampa, Florida, United States, 33613
      • USF, Department of Psychiatry and Behavioral Neurosciences
  • Illinois
    • Berwyn, Illinois, United States, 60402
      • Research Network America
    • Chicago, Illinois, United States, 60634
      • Chicago Research Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • Clinical Trials Of America
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices and Research
  • Missouri
    • O'Fallon, Missouri, United States, 63368
      • Psychiatric Care and Research Center (PCRC)
  • New York
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research LLC
    • New York, New York, United States, 10168
      • Fieve Clinical Research Inc
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center PRIME
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites LLC
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Garfield Heights, Ohio, United States, 44125
      • Charak Center for Health and Wellness
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Perelman School of Medicine
  • Texas
    • Bellaire, Texas, United States, 77401
      • West Houston Clinical Research Service
    • Fort Worth, Texas, United States, 76104
      • North Texas Clinical Trials
    • Friendswood, Texas, United States, 77546
      • Bay Area Clinical Services
    • Houston, Texas, United States, 77074
      • Clinical Trial Network - Houston
  • Utah
    • Clinton, Utah, United States, 84015
      • Alpine Research Organization
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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).	Other: Placebo; Placebo will be administered orally as tablets.
Experimental: 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).	Drug: Aticaprant; Aticaprant will be administered orally as tablets.; Other Names: JNJ-67953964

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in MADRS total score indicates improvement.	Baseline (Day 1) to Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) Total Score	The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD across the 4 domains: hobbies, social activities, food/drink, and sensory experience. The DARS scale measures desire, motivation, effort, and consummatory pleasure. The DARS is rated on a 5-point Likert scale (0=not at all, 1=slightly, 2=moderately, 3=mostly, 4=very much) and responses are summed to generate the total score (ranges from 0 to 68). A lower total score is indicative of greater anhedonia. Positive changes in DARS total score indicate improvement.	Baseline (Day 1) to Day 43
Change From Baseline Over Time in MADRS Total Score	Change from baseline over time in MADRS total score is reported. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in MADRS total score indicates improvement.	Baseline (Day 1), Days 15, 29 and 43
Percentage of Participants Who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43	Percentage of participants who achieved response on depressive symptoms scale based on MADRS total score at Day 43 are reported. Responders are defined as participants with a >=50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition.	At Day 43
Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score at Day 43	Percentage of participants with remission of depressive symptoms based on MADRS total score at Day 43 is reported. Participant is defined as a remitter at a given time point if the MADRS total score is less than or equal to (<=)10 at that time point. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition.	At Day 43
Change From Baseline to Day 43 in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score	Change from baseline to Day 43 in PHQ-9 total score is reported. 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) 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. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in PHQ-9 total score indicate improvement.	Baseline (Day 1) to Day 43
Change From Baseline Over Time in DARS Total Score	Change from baseline over time in DARS total score is reported. The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD across the 4 domains: hobbies, social activities, food/drink, and sensory experience. The DARS scale measures desire, motivation, effort, and consummatory pleasure. The DARS is rated on a 5-point Likert scale (0=not at all, 1=slightly, 2=moderately, 3=mostly, 4=very much) and responses are summed to generate the total score (range of 0 to 68). A lower total score is indicative of greater anhedonia. Positive changes in DARS total score indicate improvement.	Baseline (Day 1), Days 15, 29, and 43
Change From Baseline Over Time in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1)	Change from baseline over time in the PHQ-9 anhedonia-specific item (PHQ-9, item 1 is little interest or pleasure in doing things) is reported. 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) 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. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in PHQ-9 total score indicate improvement.	Baseline (Day 1), Day 15, Day 29, and Day 43
Percentage of Participants With a Score Less Than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43	Percentage of participants with a score <2 in the PHQ-9 anhedonia-specific item (PHQ-9, item 1 is little interest or pleasure in doing things) at Day 43 is reported. 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) 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. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27).	At Day 43
Change From Baseline Over Time in Patient Reported Outcomes Measurement Information System Short Form - Ability to Participate in Social Roles and Activities - 8a (PROMIS-APS 8a)	Change from baseline over time in the PROMIS-APS 8a is reported. This 8-item measure assesses participants' ability to participate in social roles and activities. The items measures the degree of involvement in social roles, activities, and responsibilities, including work, family, friends, and leisure. Each item is rated on a 5-point ordinal scale including 1=always, 2=usually, 3=sometimes, 4=rarely and 5=never, with higher scores indicating better social functioning. The total scores of PROMIS-APS 8a ranges from 8 to 40 and is transformed using a T-score metric with a mean of 50 and a standard deviation of 10. T-score ranges from 25.9 to 65.4, a higher score indicates better social functioning. Positive change in score indicates improvement.	Baseline (Day 1), Days 15, 29, and 43
Percent Change From Baseline Over Time in Work Productivity and Activity Impairment: Depression (WPAI:D)	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 yields four types of scores: (a) Absenteeism (work time missed); (b) Presenteeism (impairment at work / reduced on-the-job effectiveness); (c) Work productivity loss (overall work impairment / absenteeism plus presenteeism); (d) Activity Impairment. The first three scores are derived only for respondents who were working (should be missing for non-working), but the last score is applicable for all respondents. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity. Negative changes in score indicates less impairment and greater productivity.	Baseline (Day 1), Days 29 and 43
DB Treatment Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	Percentage of participants with TEAEs during DB treatment phase are reported. A TEAE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. A TEAE does not necessarily have a causal relationship with the intervention. TEAEs included both serious and non serious adverse events. TEAEs were defined as AEs with onset during the DB Treatment Phase, or AEs that are a consequence of a pre-existing condition that has worsened since baseline (Day 1).	From start of treatment (Day 1) up to Day 43
Follow-up (FU) Phase: Percentage of Participants With AEs	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	From Day 44 up to Day 57

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Actual): September 18, 2024
• Study Completion (Actual): September 18, 2024

Study Registration Dates

• First Submitted: July 10, 2022
• First Submitted That Met QC Criteria: July 10, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Estimated): November 6, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Mood Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Depressive Disorder, Major; Anhedonia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Aticaprant
• Other Study ID Numbers: CR109217; 2022-000439-22 (EudraCT Number); 67953964MDD3001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No