A Study of JNJ-61393215 in the Treatment of Depression
Condition: Major Depressive Disorder With Anxious Distress
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: JNJ-61393215; Placebo
Intervention description: JNJ-61393215 will be administrated orally.; Matching placebo will be administered orally.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 222.0
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-61393215 as adjunctive treatment
      compared to adjunctive placebo, as assessed by the change from baseline to week 6 on a
      17-item Hamilton Depression Rating Scale (HDRS-17) in participants with major depressive
      disorder (MDD) with anxious distress with a score greater than or equal to (>=) 2 on item 26
      or 27 of the Inventory of Depressive Symptomatology, Clinician Rating -30 (IDS-C30), who have
      a suboptimal response to current treatment with a standard antidepressant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have a body mass index (BMI) between 18 and 36 kilogram per meter
             square (kg/m^2)

          -  Participants must have a primary diagnostic and statistical manual of mental
             disorders, 5th edition (DSM-5) diagnosis of major depressive disorder (MDD) with
             anxious distress, as assessed by the mini international neuropsychiatric inventory
             7.0. Plus (MINI). Participants with a diagnosis of comorbid generalized anxiety
             disorder (GAD), post-traumatic stress disorder, persistent depressive disorder,
             attention deficit hyperactivity disorder (ADHD), social anxiety disorder or
             nicotine/caffeine dependence may be included, if MDD is primary diagnosis

          -  Participants must have an inventory of depressive symptomatology, clinician rating-30
             (IDS-C30) total score greater than or equal to (>=) 35 (moderate to severe depression)

          -  Participant must not have received more than 3 failed antidepressant treatments (of
             adequate dose and duration), including their current treatment, in the current episode
             of depression, as documented by the massachusetts general hospital antidepressant
             treatment history questionnaire (MGH-ATRQ)

          -  Participant must be currently receiving 1 of the following antidepressants for at
             least 6 weeks duration at screening, at an adequate therapeutic dose, as determined by
             the MGH-ATRQ and should remain on a stable dose throughout the study: bupropion,
             citalopram, escitalopram, sertraline, paroxetine, venlafaxine, desvenlafaxine,
             duloxetine, fluoxetine, vilazodone, vortioxetine, mirtazapine, agomelatine,
             nortriptyline, imipramine, amitriptyline and levomilnacipran

          -  Participants must have a suboptimal response (improvement <50%) to the antidepressant
             used as their current treatment, as measured by the MGH-ATRQ

          -  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:

          -  Participant has any other psychiatric condition including but not limited to: MDD with
             current psychotic features, bipolar disorder (including lifetime diagnosis),
             obsessive-compulsive disorder, borderline personality disorder, eating disorder
             (example: bulimia, anorexia nervosa), or schizophrenia (lifetime)

          -  Age of onset of depression is after 55 years of age

          -  Participant has a history of alcohol or substance use disorder (abuse/dependence)
             within 6 months prior to screening (nicotine and caffeine dependence are not
             exclusionary)

          -  Participant has a current or recent (within the past year) history of clinically
             significant suicidal ideation (corresponding to a score of >= 3 for ideation) or any
             suicidal behavior within the past year, as validated on the Colombia suicide severity
             rating scale (C-SSRS) at screening or baseline

          -  Length of current major depressive episode >60 months

          -  Participant has organic brain disease or dementia or has known or suspected
             intellectual development disorder

          -  Participant has been treated with at least one of the following treatments: (a)
             electroconvulsive therapy in the current episode; (b) deep brain stimulation
             (lifetime); (c) repetitive transcranial magnetic stimulation within 4 weeks prior to
             baseline visit

          -  Participant has any clinically relevant medical condition that could potentially alter
             the absorption, metabolism, or excretion of the study intervention, such as liver
             disease or renal disease

          -  Participant has a relevant history of any significant and/or unstable cardiovascular,
             respiratory, neurological (including seizures - uncomplicated childhood febrile
             seizures with no sequelae are not exclusionary) or significant cerebrovascular, renal,
             hepatic, dermatologic, hematologic, gastrointestinal or endocrine diseases.
             Hospitalization for cardiovascular event (myocardial infarction, unstable angina,
             stroke, transient ischemic attack) within 3 months prior to the first administration
             of study drug is exclusionary. Diabetes mellitus be allowed when the participant is
             stable (HbA1c less than 7.5% or 58 mmol/mol)

          -  Participant has a clinically significant abnormal physical examination, vital signs or
             12-lead electrocardiogram (ECG) at screening or baseline Minor deviations in ECG,
             which are not considered to be of clinical significance to the investigator, are
             acceptable.If at screening visit QTcB or QTcF interval >=450 ms for males or >=470 ms
             for females, or >480 ms if bundle branch block and prolongation of the QTc interval
             are present;participant is excluded

          -  Participant has a history of known demyelinating diseases such as multiple sclerosis
             or optic neuritis