A Study to Investigate the Safety, Tolerability, and Pharmacodynamics of JNJ-54175446 in Participants With Major Depressive Disorder

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Safety, Tolerability, and Pharmacodynamics of JNJ-54175446 in Subjects With Major Depressive Disorder

The primary purpose of this study is to investigate the safety and tolerability of JNJ 54175446 in participants with Major Depressive Disorder (MDD).

Inclusion Criteria:

• Body mass index (BMI) must be between 18 and 32 kilogram per square meter (kg/m^2) inclusive
• Related to symptoms of depression: Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V diagnostic criteria for Major Depressive Disorder [MDD] (International Classification of Diseases (ICD)-code F32.x and F33.x), without psychotic features, as confirmed by the MINI 6.0; participant must have an IDS-C30 total score greater than or equal to (>=) 30 using the semi-structured interview guide for the IDS-C30
• Participant is, during this episode of depression, treatment naïve OR treated with at most one Selective serotonin reuptake inhibitor (SSRI) over a minimum of 6 weeks and a maximum of 6 months, and subject is being treated at an adequate dose, showing a partial response at enrolment
• A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test upon admission
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after receiving the last dose of study drug

Exclusion Criteria:

• Has a primary DSM-IV or V diagnosis of general anxiety disorder (GAD), panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, anorexia nervosa, or bulimia nervosa. Participants with comorbid GAD, social anxiety disorder, or panic disorder for whom MDD is considered the primary diagnosis are not excluded
• Has a length of current major depressive episode greater than (>) 24 months despite adequate treatment
• Has failed more than 2 treatments with a different pharmacological mode of action despite an adequate dose and duration during a previous, or the current depressive episode
• Participant has a history of substance use disorder according to DSM-V criteria, except nicotine or caffeine, within 6 months before Screening. However, participants who have completed a treatment for (alcohol) addiction more than 8 weeks prior to first dose administration and are under continuous control of the study center, may be included if the risk to fall back is considered minimal and no significant abnormalities are shown in clinical laboratory or other predose safety assessments
• Obstructive sleep apnea/hypopnea (apnea/hypopnea index >10) or restless legs syndrome (periodic leg movements with arousal index >15) as assessed on the first or second polysomnography (PSG) recording during screening