A Study of Aticaprant 10 Milligrams (mg) as Adjunctive Therapy in Adult Participants With MDD With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy
- Conditions
- Depressive Disorder, MajorAnhedonia
- Interventions
- Drug: AticaprantOther: Placebo
- Registration Number
- NCT05550532
- 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 MDD with ANH+. The total duration of the study will be up to 87 days. Safety evaluation 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
- RECRUITING
- Sex
- All
- Target Recruitment
- 710
- 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 (that is, an improvement of more than 20 percent [%] on their HDRS-17 total score) 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 structural 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
- 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 (at or above the minimum therapeutic dose per Massachusetts General Hospital Antidepressant Treatment Response Questionnaire [MGH-ATRQ] 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 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 diagnostic and statistical manual of mental disorders-5th edition (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 (that is, at least 7 treatments), 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 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent), 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 diagnostic and statistical manual of mental disorders-5th edition (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 major depressive disorder (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 10 milligrams (mg) tablet orally, once daily for 42 days during double-blind (DB) treatment phase in addition to their current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy. Participants who will complete the DB 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 tablet orally, once daily for 42 days during DB treatment phase in addition to their current antidepressant SSRI/SNRI therapy. Participants who will complete the DB 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-Asberg 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 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 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 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).
Percentage of Responders on Depressive Symptoms Scale from Baseline to Day 43 as Assessed by MADRS Total Score 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 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 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 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 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. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the 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 Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Ability to Participate in Social Roles and Activities 8a (PROMIS-APS 8a) 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 at Day 43 as Assessed by MADRS Total Score Day 43 Percentage of participants with remission of depressive symptoms, defined as a MADRS total score of 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.
Trial Locations
- Locations (129)
Centro Medico Luquez
🇦🇷Cordoba, Argentina
INSA Instituto de Neurociencias San Agustín
🇦🇷La Plata, Argentina
Clinica Privada de Salud Mental Santa Teresa de Ávila
🇦🇷La Plata, Argentina
Psychiatricka ambulance, MUDr. Marta Holanova
🇨🇿Brno, Czechia
Neuroterapie KH S R O
🇨🇿Kutna Hora, Czechia
Medical Services Prague S R O
🇨🇿Praha 6, Czechia
Institut Neuropsychiatricke pece
🇨🇿Praha 8, Czechia
CHU de Brest - Hopital de la Cavale Blanche
🇫🇷Bohars, France
CHU Clermont-Ferrand - Hopital Gabriel Montpied
🇫🇷Clermont Ferrand, France
Cabinet Medical des Drs Prizac-Desbonnet Scottez
🇫🇷Douai, France
CHU de Nantes hotel Dieu
🇫🇷Nantes, France
Hopital Sainte Anne
🇫🇷Paris, France
CHRU de Tours Clinique Psychiatrique Universitaire
🇫🇷Tours cedex 9, France
Bucheon St. Mary's Hospital
🇰🇷Bucheon-si, Korea, Republic of
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zheng Zhou, China
Instituto Medico DAMIC
🇦🇷Cordoba, Argentina
XiAn Mental Healthcare Center
🇨🇳XI An, China
CDC Research Institute LLC
🇺🇸Port Saint Lucie, Florida, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Sunwise Clinical Research
🇺🇸Lafayette, California, United States
Pacific Neuropsychiatric Specialists
🇺🇸Orange, California, United States
Prospective Research Innovations Inc
🇺🇸Rancho Cucamonga, California, United States
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
CMB Clinical Trials
🇺🇸Santee, California, United States
California Neuroscience Research
🇺🇸Sherman Oaks, California, United States
Pacific Clinical Research Medical Group
🇺🇸Upland, California, United States
Next Level Clinical Trials, LLC
🇺🇸West Covina, California, United States
MCB Clinical Research Centers LLC
🇺🇸Colorado Springs, Colorado, United States
LCC Medical Research Institute Inc
🇺🇸Miami, Florida, United States
Florida Research Center Inc.
🇺🇸Miami, Florida, United States
CNS Clinical Research Group
🇺🇸Coral Springs, Florida, United States
Sarkis Clinical Trials
🇺🇸Gainesville, Florida, United States
K2 Medical Research
🇺🇸Maitland, Florida, United States
Vital Care Research
🇺🇸Miami, Florida, United States
Global Medical Institutes
🇺🇸Moosic, Pennsylvania, United States
Ezy Medical Research
🇺🇸Miami, Florida, United States
Felicidad Medical Research
🇺🇸Miami, Florida, United States
Bravo Health Care Center
🇺🇸North Bay Village, Florida, United States
APG Research LLC
🇺🇸Orlando, Florida, United States
Combined Research Orlando
🇺🇸Orlando, Florida, United States
Quantum Laboratories
🇺🇸Pompano Beach, Florida, United States
CEN Consultorios Especializados en Neurociencias
🇦🇷Cordoba, Argentina
Psychiatric Medicine Associates
🇺🇸Skokie, Illinois, United States
Tandem Clinical Research
🇺🇸Marrero, Louisiana, United States
CBH Health
🇺🇸Gaithersburg, Maryland, United States
Michigan Clinical Research Institute
🇺🇸Ann Arbor, Michigan, United States
Revive Research Institute
🇺🇸Farmington Hills, Michigan, United States
Midwest Research Group
🇺🇸Saint Charles, Missouri, United States
Premier Psychiatric Research Institute, LLC
🇺🇸Lincoln, Nebraska, United States
Erie County Medical Center
🇺🇸Buffalo, New York, United States
Manhattan Behavioral Medicine
🇺🇸New York, New York, United States
New Hope Clinical Research
🇺🇸Charlotte, North Carolina, United States
Monroe Biomedical Research
🇺🇸Monroe, North Carolina, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Wexner Medical Center at the Ohio State University
🇺🇸Columbus, Ohio, United States
Conrad Clinical Research
🇺🇸Edmond, Oklahoma, United States
Sooner Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
Paradigm Research Professionals, LLC
🇺🇸Oklahoma City, Oklahoma, United States
Lehigh Center for Clinical Research
🇺🇸Allentown, Pennsylvania, United States
Donald J Garcia Jr MD PA
🇺🇸Austin, Texas, United States
Relaro Medical Trials
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
R and H Clinical Research
🇺🇸Stafford, Texas, United States
Cedar Psychiatry
🇺🇸Murray, Utah, United States
Northwest Clinical Research Center
🇺🇸Bellevue, Washington, United States
Core Clinical Research
🇺🇸Everett, Washington, United States
Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
C I A P Centro de investigacion y Asistencia en Psiquiatria
🇦🇷Rosario, Argentina
Clinica Mayo de UMCB
🇦🇷San Miguel de Tucuman, Argentina
Clinica El Jardin
🇦🇷Santiago del Estero, Argentina
Trial Tech Tecnologia em Pesquisas com Medicamentos
🇧🇷Curitiba, Brazil
Associacao Hospitalar Moinhos de Vento
🇧🇷Porto Alegre, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos
🇧🇷São Bernardo do Campo, Brazil
MHC - Sofia, EOOD
🇧🇬Sofia, Bulgaria
DCC 'Sv. Vrach and Sv. Sv. Kuzma and Damyan', OOD
🇧🇬Sofia, Bulgaria
Medical Center Hera EOOD
🇧🇬Sofia, Bulgaria
Diagnostic Consulting Center Mladost - M Varna
🇧🇬Varna, Bulgaria
Medical Center Intermedica, OOD
🇧🇬Sofia, Bulgaria
DIEX Recherche Sherbrooke Inc
🇨🇦Sherbrooke, Quebec, Canada
Alpha Recherche Clinique
🇨🇦Quebec, Canada
Hebei Mental Health Center
🇨🇳Baoding, China
Beijing Anding Hospital of Capital Medical University
🇨🇳Beijing, China
Beijing Huilongguan Hospital
🇨🇳Beijing, China
Peking University Sixth Hospital
🇨🇳Beijing, China
The second Xiangya Hospital of Central South University
🇨🇳Changsha, China
West China Hospital Sichuan University
🇨🇳Chengdu, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
Huzhou third people's Hospital
🇨🇳Hu Zhou, China
Shanghai Mental Health Center
🇨🇳Shanghai, China
Tongji Hospital of Tongji University
🇨🇳Shanghai, China
The First Hospital of Hebei Medical University
🇨🇳Shijiazhuang, China
Suzhou Guangji Hospital
🇨🇳Suzhou, China
Tianjin Anding Hospital
🇨🇳Tianjin, China
Wuhan Mental Health Center
🇨🇳Wuhan, China
Wuhu Hospital of Beijing Anding hospital
🇨🇳Wuhu, China
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
CHA University ilsan Medical Center
🇰🇷Goyang, Korea, Republic of
Korea University Ansan Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
KyungHee University Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Yeouido St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Clinsante Osrodek Badan Klinicznych
🇵🇱Bydgoszcz, Poland
Centrum Medyczne Care Clinic Katowice
🇵🇱Katowice, Poland
Filip Rybakowski Specjalistyczna Praktyka Lekarska
🇵🇱Poznan, Poland
Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger Molenda
🇵🇱Suchy Las, Poland
Psychomed-Svatosavsky, s.r.o.
🇸🇰Banska Bystrica, Slovakia
Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach
🇸🇰Bojnice, Slovakia
Psychiatricka Ambulancia Mentum S.R.O.
🇸🇰Bratislava, Slovakia
Epamed sro
🇸🇰Koshice, Slovakia
Univerzitna nemocnica L. Pasteura Kosice
🇸🇰Kosice, Slovakia
Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu
🇸🇰Liptovsky Mikulas, Slovakia
Psychiatricka Ambulancia Psycholine S.R.O.
🇸🇰Rimavska Sobota, Slovakia
Crystal Comfort s.r.o.
🇸🇰Vranov nad Toplou, Slovakia
Cape Town Clinical Research Centre
🇿🇦Cape Town, South Africa
Gert Bosch Pretoria South Africa
🇿🇦Pretoria, South Africa
Somerset West Clinical Research Unit
🇿🇦Strand, South Africa
China Medical University Hospital
🇨🇳Taichung, Taiwan
University of Sussex
🇬🇧Brighton, United Kingdom
Royal Edinburgh Hospital
🇬🇧Edinburgh, United Kingdom
Taipei Medical University
🇨🇳Taipei City, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Cheng Hsin General Hospital
🇨🇳Taipei, Taiwan
Institute of Psychiatry
🇬🇧London, United Kingdom
Renfrewshire CMHT
🇬🇧Paisley, United Kingdom
Moorgreen Hospital
🇬🇧Southampton, United Kingdom
Crisis Resolution and Home Treatment Team
🇬🇧Wigan And Leigh, United Kingdom
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