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

Hamilton Depression Rating Scale 17 (HDRS17) contains 17 items pertaining to symptoms of depression experienced over the past week. Score range is from 0 to 52. The Inventory of Depressive Symptomatology- Clinician rated-30 (IDS-C30) is a standardized 30 item, clinician rated, scale to assess the severity of a participant's depressive symptoms. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression.

The QIDS-SR16 (1 week recall period) is a participant reported measure designed to assess the severity of depressive symptoms. The total score ranges from 0 to 27 (none 1-5, mild 6-10, moderate 11-15, severe 16-20 and very severe 21-27). QIDS-SR10 is a version of the QIDS-SR16 with a shorter, 2-hour recall period and 10-item measure. Scoring for each domain will be the same as for the QIDS-SR16.

Latency to persistent sleep is defined as the length of time from full wakefulness to the first sleep stage.

All of the minutes of Stages 1, 2, 3/4 Non Rapid Eye-Movement (NREM) and Rapid-Eye-Movement (REM) sleep, as measured by Polysomnography, are summed to determine the Total Sleep Time.

The number of minutes in the Awake stage after the onset of persistent sleep to the end of the recording.

The total sleep time divided by the total time in bed (that is, the number of minutes from the beginning of the Polysomnography recording to the end of the recording).

The SHAPS is a short, 14-item instrument to measure anhedonia, which has been shown to be valid and reliable in normal and clinical samples. Each of the 14 items has a set of four response categories: Definitely Agree (= 1), Agree (= 2), Disagree (= 3), and Definitely Disagree (= 4). A higher total score indicates higher levels of state anhedonia.

The POMS measures individuals' mood states. The POMS consists of 30 positive and negative mood descriptors. Participants are asked to rate, on a 5-point scale from 0 (not at all) to 4 (extremely), the extent to which they experience each mood state during at a specific moment.

Evaluation of positive and negative effect using emotional faces recognition test. The participant is seated at a computer screen and instructed to remember 42 images shown during a training session. Subject then identifies those images during a testing session in which the 42 probe images are interspersed among 42 additional foil images. Implicit recognition is detected by EEG.

Performance will be scored after a fixed period of 3.5 minutes and reflected visuo motor control and vigilance. The average performance scores will be used in the analysis.

An implicit image recognition (IR) task combined with emotional elicitation evaluates attention, encoding and image recognition memory during implicit emotion elicitation.

The Cmax is the maximum observed plasma concentration.

Minimum observed plasma concentration during dosing interval (tau).

The observed plasma concentration just prior to the beginning or at the end of a dosing interval of any dose other than the first dose.

Average plasma concentration at steady state over the dosing interval.

Apparent elimination half-life associated with the terminal slope (Lambda[z]) of the semilogarithmic drug concentration time curve, after multiple-dose administration only.

The ratio of the maximum plasma concentration (Peak) to trough observed concentration.

Accumulation ratio based on AUC, determined after multiple-dose administration and calculated as AUCtau on Day 1 divided by AUCtau on Day 10.

The reward task was a probabilistic instrumental learning task involving monetary wins or losses. In order to maximize payoffs, participants should use the outcome feedback to gradually learn the symbol-outcome associations by trial and error over time, such that they consistently choose the symbol with the high-probability win and avoid the symbol with the high-probability loss. Outcome measures included overall total, total won and lost, choice frequency, percentage of choices identical to the preceding one (percentage consistency), reaction time and re-reaction time.