A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: JNJ-42847922; Placebo Matching to JNJ-42847922; Quetiapine XR; Placebo Matching to Quetiapine XR; Selective Serotonin Reuptake Inhibitor (SSRI); Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)
Intervention description: Participants will receive JNJ-42847922 capsule orally.; Participants will receive placebo capsule matching to JNJ-42847922 orally.; Participants will receive quetiapine XR capsule orally.; Participants will receive placebo capsule matching to quetiapine XR orally.; Participants will receive SSRI antidepressant (such as, citalopram, escitalopram, fluvoxamine, fluoxetine, paroxetine, sertraline, vilazodone or vortioxetine) as a part of background therapy (at the same dose, without change, every day and at approximately the same time as prior to entering the study) throughout the screening, double-blind, and follow-up phases (approximately up to Week 26).; Participants will receive SNRI antidepressant (such as duloxetine, milnacipran, levomilnacipran, venlafaxine, desvenlafaxine) as a part of background therapy (at the same dose, without change, every day and at approximately the same time as prior to entering the study) throughout the screening, double-blind, and follow-up phases (approximately up to Week 26).
Intervention MeSH terms: Norepinephrine; Quetiapine Fumarate; Serotonin; Selective Serotonin Reuptake Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the efficacy of flexibly dosed JNJ-42847922 (20
      milligram [mg] or 40 mg) compared to flexibly dosed quetiapine extended-release (XR) (150 mg
      or 300 mg) as adjunctive therapy to an antidepressant drug in delaying time to all-cause
      discontinuation of study drug over a 6-months (24 weeks) treatment period, in participants
      with major depressive disorder (MDD) who have had an inadequate response to current
      antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or
      serotonin-norepinephrine reuptake inhibitor (SNRI).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female of non-childbearing potential (WONCBP) outpatients, aged 18 to 70 years
             (inclusive). A WONCBP is defined as: a).Postmenopausal: A postmenopausal state is
             defined as no menses for 12 months without an alternative medical cause. b).
             Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral
             salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral
             oophorectomy. c). If reproductive status is questionable, additional evaluation should
             be considered

          -  Meet Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5)
             diagnostic criteria for 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). The length of the current
             depressive episode must be less than or equal to (<=) 18 months

          -  Have had an inadequate response to at least 1 but no more than 3 antidepressants,
             administered at an adequate dose and duration in the current episode of depression, as
             assessed by the Massachusetts General Hospital-Antidepressant Treatment Response
             Questionnaire (MGH-ATRQ). An inadequate response is defined as less than (<)50 percent
             (%) reduction in depressive symptom severity, as assessed by the MGH-ATRQ. An adequate
             trial is defined as an antidepressant treatment for at least 4 weeks at or above the
             minimum therapeutic dose, as specified in the MGH-ATRQ, for any particular
             antidepressant. The inadequate response must include the participant's current
             antidepressant treatment

          -  Be receiving monotherapy treatment for depressive symptoms with 1 of the following
             selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake
             inhibitor (SNRI) antidepressants, in any formulation: citalopram, duloxetine,
             escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine,
             sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose
             (at or above the minimum therapeutic dose level) for at least 4 weeks, and for no
             greater than 12 months, at screening. Modification of an effective preexisting therapy
             should not be made for the explicit purpose of entering a participant into the study

          -  Have a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than or
             equal to (>=)25 (performed by independent, centralized remote raters) at screening and
             must not demonstrate a clinically significant improvement (that is, an improvement of
             greater than (>)20% on their MADRS total score) from the screening to baseline visit

          -  Have a Body Mass Index (BMI) between 18 and 35 kilogram per meter square (kg/m^2)
             inclusive (BMI equal to [=] weight/height^2)

          -  Must be otherwise healthy on the basis of physical examination, medical history, vital
             signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at
             screening. If there are abnormalities, they must be consistent with the underlying
             illness in the study population. If the results of the clinical laboratory tests are
             outside the normal reference ranges, the participant may be included only if the
             investigator judges the abnormalities or deviations from normal to be not clinically
             significant or to be appropriate and reasonable for the population under study. This
             determination must be recorded in the participant's source documents and initialed by
             the investigator

        Exclusion Criteria:

          -  Have Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of
             significant medical disorders of the hypothalamic-pituitary-adrenal (HPA) axis

          -  Have a history of epilepsy, neuroleptic malignant syndrome (NMS) or Tardive Dyskinesia

          -  Have a history of previous non-response to an adequate trial of quetiapine as an
             adjunctive treatment for MDD (adequate trial defined as >=150 mg for 4 weeks or more)
             and/or a history of lack of response to 3 or more adequate antidepressant treatments
             and/or a history or evidence of noncompliance with current antidepressant therapy

          -  Have taken a known moderate or strong inhibitor/inducer of cytochrome P450 (CYP)3A4
             and CYP2C9 or a dual inhibitor/inducer of CYP3A4 and CYP2C9 within 14 days (or after
             washout that is, duration of 5 times the drug's half-life) before the first study drug
             administration on Day 1 until the follow-up visit. Fluvoxamine is a moderate CYP2C9
             inhibitor and a mild CYP3A inhibitor, and will not be excluded from the study

          -  Have a history or current diagnosis of a psychotic disorder, bipolar disorder,
             intellectual disability, autism spectrum disorder, borderline personality disorder,
             somatoform disorders, or fibromyalgia