Clinical trial NCT03227224 (phase 2, status: completed)
Conditions: depressive disorder, major
ICD codes: F33.0, F33.1, F33.9, F32.0, F32.1, F32.9, F33.40
Drugs: placebo, jnj-42847922
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Men or women of non-childbearing potential (WONCBP), 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). In addition their major
             depressive episode must be deemed "valid" using the SCID Screening Questionnaire (SSQ)
             interview administered by remote, independent raters. 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
             measured 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 specified in the MGH-ATRQ, for any particular antidepressant.
             The inadequate response must include the participant's current antidepressant
             treatment

          -  Participants receiving monotherapy treatment for depressive symptoms with one of the
             following selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake
             inhibitor (SSRI/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 subject 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

          -  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 the results of the clinical laboratory tests are outside the normal
             reference ranges, the participant could 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:

          -  Has a history of, or current signs and symptoms of, severe renal insufficiency
             (creatinine clearance <30 milliliter per minute [mL/min]); moderate to severe hepatic
             insufficiency (Child-Pugh Score 7-9), significant or unstable cardiovascular,
             respiratory, gastrointestinal, neurologic (including narcolepsy), hematologic,
             rheumatologic, immunologic or endocrine disorders (including uncontrolled hypo- or
             hyperthyroidism or diabetes, or insulin-dependent diabetes mellitus). Participants
             with non-insulin dependent diabetes mellitus who are well-controlled (hemoglobin A1C
             [HbA1C] <=7.5% and fasting glucose <126 milligram per deciliter [mg/dL] at screening)
             could be eligible to participate if otherwise medically healthy, and if on a stable
             regimen of glucose-lowering medications for at least 2 months prior to screening

          -  Has signs and symptoms of Cushing's Disease, Addison's Disease, primary amenorrhea, or
             other evidence of significant medical disorders of the hypothalamic-pituitary-adrenal
             (HPA) axis

          -  Has a history of lack of response to 3 or more adequate antidepressant treatments, as
             indicated by no or minimal (<= 25% improvement in symptoms) when treated with an
             antidepressant of adequate dose (per MGH-ATRQ) and duration (at least 4 weeks)

          -  Has history or current diagnosis of a psychotic disorder, bipolar disorder, mental
             retardation, autism spectrum disorder, or borderline personality disorder, somatoform
             disorders, chronic fatigue syndrome or fibromyalgia

          -  Has any significant primary sleep disorder, including but not limited to obstructive
             sleep apnea, restless leg syndrome, or parasomnias