A Study to Explore the Efficacy of JNJ-67953964 in the Treatment of Depression
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: JNJ-67953964; Placebo
Intervention description: JNJ-67953964 10 mg will be administered as two 5-mg capsules orally once daily.; Matching placebo will be administered as 2 capsules orally once daily.
Intervention MeSH terms: Aticaprant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 181.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy of JNJ-67953964 compared to placebo
      when administered as adjunctive treatment in participants with Major Depressive Disorder
      (MDD) partially responsive to selective serotonin reuptake inhibitor/
      serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) treatment in terms of reduction of
      symptoms of depression, as assessed by the change from baseline on the Montgomery Asberg
      Depression Rating Scale (MADRS) in non-responders during the placebo lead-in period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a Body Mass Index (BMI) between 18 and 35 kilogram per meter square (kg/m^2)
             inclusive (BMI = weight/height^2)

          -  Participants must be medically stable based on clinical laboratory tests, medical
             history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and
             baseline

          -  Participants must have a primary Diagnostic and Statistical Manual of Mental Disorders
             5th edition (DSM-5) diagnosis of Major Depressive Disorder (MDD)

               1. The current episode should be less than 18 months

               2. Participants should be currently treated with an SSRI or SNRI at an adequate dose
                  and for at least 6 weeks but no more than 12 months

               3. Have a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than
                  or equal to (>=) 25 at screening

          -  A woman of childbearing potential must have a negative serum pregnancy test at
             screening and a negative urine pregnancy test before the first dose

        Exclusion Criteria:

          -  History of documented gastric disease (including documented peptic ulcer disease,
             gastritis, upper gastrointestinal [GI] bleeding, esophagitis, or any GI precancerous
             condition), current clinically evident GI complaints

          -  Chronic use of a proton pump inhibitors (PPIs). History of incidental use of PPIs is
             allowed but should have been stopped at least 4 weeks before screening. A history of
             chronic nonsteroidal anti-inflammatory drug (NSAID) or aspirin use. (Low dose aspirin
             for example in cardiovascular disease prevention is allowed)

          -  Has a history of alcohol use disorder within the past year

          -  Has failed (no more than 25 percent [%] response on Antidepressant Treatment History
             Questionnaire [ATRQ]) three or more antidepressant treatments including the current
             Selective serotonin reuptake inhibitor/ serotonin-norepinephrine reuptake inhibitor
             (SSRI/SNRI) during the current depressive episode despite an adequate dose (per ATRQ)
             and duration (at least 6 weeks)

          -  Has signs or symptoms of Cushing's Disease, Addison's Disease, primary amenorrhea, or
             other evidence of significant medical disorders of the hypothalamus pituitary adrenal
             (HPA) axis

          -  Participant has received an investigational drug (including investigational vaccines)
             or used an invasive investigational medical device within 3 months before the planned
             first dose of study drug or has participated in any interventional clinical studies on
             MDD in the previous 1 year or is currently enrolled in an interventional study

          -  Has one or more of the following diagnoses:

               1. A primary DSM (5th edition) diagnosis of generalized anxiety disorder (GAD),
                  panic disorder, obsessive compulsive disorder (OCD), posttraumatic stress
                  disorder (PTSD). Participants with comorbid GAD, social anxiety disorder (SAD),
                  or panic disorder for whom MDD is considered the primary diagnosis are not
                  excluded

               2. A current diagnosis or diagnosis in the past 1 year of psychotic disorder, MDD
                  with psychosis, anorexia nervosa or bulimia nervosa, chronic fatigue syndrome,
                  bipolar disorder (BD), mental retardation, antisocial or borderline personality
                  disorder, autism spectrum disorder

          -  Has a current or recent history of clinically significant suicidal ideation within the
             past 6 months, corresponding to a score of 4 (active suicidal ideation with some
             intent to act, without specific plan) or 5 (active suicidal ideation with specific
             plan and intent) for ideation on the Colombia suicide severity rating scale (C-SSRS),
             or a history of suicidal behavior within the past 1 year

          -  Ongoing psychological treatments (example, Cognitive Behavior Therapy, Interpersonal
             Psychotherapy, Psychodynamic Psychotherapy, etcetera [etc.]), initiated within 1 month
             prior to the screening phase. A participant who has been receiving ongoing
             psychological treatment for a period of greater than 1 month from the screening visit
             is eligible, if the investigator deems the psychological treatment to be of stable
             duration and frequency

          -  Participant has a history of substance use disorder according to DSM-5 criteria,
             except nicotine or caffeine, within 6 months before screening. Mild cases can be
             reviewed on a case by case basis. Participants who have completed a treatment for
             (alcohol) addiction more than 1 year prior to first dose administration, may be
             included if the risk of relapse is considered minimal, total duration of alcohol use
             disorder was less than a year, and no significant abnormalities are shown in clinical
             laboratory or other pre-dose safety assessments

          -  Participant has used:

               1. Monoamine oxidase inhibitors (MAOIs) within 12 weeks before screening

               2. St. John's wort, ephedra, ginkgo, ginseng, or kava within 2 weeks before
                  screening

               3. Antipsychotic drugs (D2-antagonists) within 2 weeks before screening. However,
                  Seroquel (quetiapine) in a dose less than or equals to (<=)100 milligram (mg) is
                  allowed when used in a stable dose for at least 8 weeks prior to screening.
                  Quetiapine treatment should be continued unchanged during the study

               4. Opioids within 2 weeks before screening

               5. Psychostimulants such as methylphenidate or dextroamphetamine within 2 weeks
                  before screening

               6. Psychotropics with antidepressant effects such as atomoxetine or thyroid
                  supplementation, in addition to their SSRI or SNRI treatment within 2 weeks
                  before screening

          -  Participant is unable to stop the following medication from the baseline visit (Visit
             2) and throughout the study (tapering during screening period allowed): Any hypnotics
             including but not limited to: i. Benzodiazepines when used only as needed (PRN) are
             not allowed ii. Sedating antihistamines, including chronic use of diphenhydramine iii.
             Continuous use of zolpidem, zoplicon, eszopiclone and ramelteon. Note:
             Nonbenzodiazepines sleep aids (including: zolpidem, zaleplon, and eszopliclone) are
             allowed on an as needed (PRN) basis during the study but NOT within 24 hours before
             being in the clinic and not more than 2 nights in a row iv. S-adenosyl methionine
             (SAMe) v. Melatonin, agomelatine

          -  Has received any prior treatment with electroconvulsive therapy, vagal nerve
             stimulation, or a deep brain stimulation device or treatment with ketamine or
             esketamine for MDD