A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-55375515 in Healthy Male Participants

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

The Effect of JNJ-55375515 on slow wave activity recorded by the electroencephalogram (EEG) will be evaluated. EEG recordings are made using gold electrodes, fixed at Midline Frontal Electrode (Fz), Midline Central Electrode (Cz), Midline Parietal Electrode (Pz) and Midline Occipital Electrode (Oz), with the same common ground electrode as for the eye movement registration (international 10/20 system). Per session eight consecutive blocks of eight seconds are recorded. For each lead, fast Fourier transform analysis will be performed to obtain the sum of amplitudes in the very low (0.5-2 Hertz [Hz]), delta- (2-4 Hz), theta (4-7.5 Hz), alpha- (7.5-13.5 Hz), beta- (13.5-35 Hz), and gamma-(35-48.9 Hz) frequency ranges. The total test will last approximately 2 minutes.

Heart rate variability (HRV) is the physiological phenomenon of variation in the time interval between heartbeats. It is measured by the variation in the beat-to-beat interval. HRV will be derived from Holter recordings. Holter recordings will start pre dose on Day 1 of each period in Part 1 and continue for 24 hours. Measurements will be made at rest (during 5 minutes) and HRV parameters will be derived from these 5-minute recordings and from the 24-hour recordings.

Saccadic eye movements will be recorded to measure saccadic reaction time (RT). The recording and analysis of saccadic eye movements is performed using a computer-based system for sampling and analysis of eye movements. In a typical test system, electrodes are applied on the forehead and beside the lateral canthi of both eyes of the participant for registration of the electro-oculographic signals. Head movements are restrained using a fixed head support. The target consists of a moving dot that is displayed on a computer screen. Fifteen saccades are recorded with inter-stimulus intervals varying randomly between 3 and 6 seconds. Average values of latency (reaction time) of all correct saccades will be assessed.

Saccadic eye movements will be recorded to measure saccadic peak velocity (SPV). The recording and analysis of saccadic eye movements is performed using a computer-based system for sampling and analysis of eye movements. In a typical test system, electrodes are applied on the forehead and beside the lateral canthi of both eyes of the participant for registration of the electro-oculographic signals. Head movements are restrained using a fixed head support. The target consists of a moving dot that is displayed on a computer screen. Fifteen saccades are recorded with inter-stimulus intervals varying randomly between 3 and 6 seconds. Average values of saccadic peak velocity of all correct saccades will be assessed.

The body sway meter allows measurement of body movements in a single plane, providing a measure of postural stability. Body sway may be measured with a pot string meter (Celesco) based on the Wright ataxiameter or platform. Participants will be instructed to wear a pair of comfortable, low-heeled shoes on each session. The total period of body-sway measurement will be 2 minutes.

The KSS is a patient reported assessment of drowsiness level at the time of scale administration. This scale is focused mainly on the propensity to fall asleep and has a high validity in assessing sleepiness. It consists of a 9-point Likert scale with response options from: 1=very alert, 3=alert, 5=neither alert nor sleepy, 7=sleepy (but not fighting sleep), 9=very sleepy (fighting sleep).

The Bond and Lader Visual Analogue Scale consists of sixteen 100 millimeter (mm) visual analog scales anchored by antonyms (example, Alert-Drowsy, Lethargic-Energetic, etc). Scores will be combined to form three mood factors: alertness, calmness, and contentedness.

To establish diurnal levels of cortisol levels, repeated serum samples will be obtained throughout the Day 1 of each period. The diurnal cortisol levels will be explored to further clarify the effect of the compound on the hypothalamic-pituitary-adrenal-axis.

In this motivational processing task, participants with depressive symptoms may show a lower response bias towards a reward compared to healthy participants. The PILT allows the objective assessment of participants propensity to modulate behavior as a function of reward.

The International Shopping List Test is a measure of Verbal Memory-Learning. The test measures total number of correct responses remembering the 16-word list on three consecutive learning trials. Higher score indicates better performance.

Groton Maze Learning Task is a measure of Executive Function and Spatial Learning. The test measures total number of errors made while locating and learning 28 step pathway hidden beneath a 10*10 grid on 5 consecutive trials during a single session. Lower score indicates better performance.

To evaluate social and emotional cognition, a series of tests will be used to quantify both the ability to empathize and understand the emotions of others, and the ability to interpret their thoughts and intentions. A classical test involves the presentation of facial expressions and is asked to choose which word best describes what the person in the image is thinking or trying.

Detection task is a measure of Psychomotor Function. The test measures speed of performance; mean of the log10 transformed reaction times for correct responses. Lower score indicates better performance.

Identification task is a measure of Attention. The test measures speed of performance; mean of the log10 transformed reaction times for correct responses. Lower score indicates better performance.

One back task is a measure of Working Memory. The test measures speed of performance; mean of the log10 transformed reaction times for correct responses. Lower score indicates better performance.

International shopping list test - Delayed Recall is a measure of Delayed Verbal Memory. The test measures total number of correct responses recalling the 16 words learned previously after a delay. Higher score indicates better performance.

Groton Maze Learning - Delayed recall is a measure of Delayed Spatial Memory. The test measures number of errors made while locating 28 step pathway hidden beneath a 10*10 grid after a delay. Lower score indicates better performance.

The induced stress test consists of a highly demanding computer task that is performed for 20 minutes.

LPS is the time in minutes from 'lights out' that marks the starting of total recording time to the first epoch scored as sleep.

Polysomnographic recordings will be used to determine the total time spent in deep sleep (duration of slow wave sleep) -stage 3 sleep by 8-hour overnight.

Polysomnographic recordings will be used to determine the time in bed by 8-hour overnight.

The Continuous Paired Associate Learning (CPAL) test will be used to assess whether JNJ-55375515 will improve performance of complex cognitive tasks. CPAL assess Visual episodic memory (associate learning) cognitive domain. In this task, participants must learn a series of associations between a set of difficult to verbalize patterns (amoeba) and locations. In healthy adults, 14 pattern/location associations must be learned. In the presentation phase of the task the pattern appears at the location and the participant is required to acknowledge that they have seen the pattern by touching the location at which it appears. Patterns are presented in random order. In the learning phase of the task, participants must place each of the 14 patterns in their correct locations. They must do this in 10 rounds. Number of errors made in correctly placing each of the four patterns in their location four times. (Lower score = better performance).

Cmax is the maximum observed plasma concentration.

Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

AUC(0-last) is area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentrations.