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

Janssen Research & Development, LLC42 enrolled

Overview

The purpose of this study is to assess safety and tolerability of day-time and night-time dosing of JNJ-55375515 in healthy male participants.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

JNJ-55375515 Dose Level 1DRUG

Participants will receive JNJ-55375515 orally at a Dose level 1 in Part 1 of study.

JNJ-55375515 Dose Level 2DRUG

Participants will receive JNJ-55375515 orally at a Dose level 2 in Part 1 of study.

JNJ-55375515 Dose Level 3DRUG

Participants will receive JNJ-55375515 orally at a Dose level 3 in Part 1 of study.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 54 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Body Mass Index (BMI) between 18 and 30 kilogram / square meter (kg/m\^2) inclusive (BMI=weight/height\^2) * Participant must be healthy based on clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, coagulation or urinalysis are outside the normal reference ranges, retesting of an abnormal lab value (s) that may lead to exclusion will be allowed once during the screening phase. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable * Participant must be healthy based on physical and neurological examination, medical history, vital signs, and 12-lead Electrocardiography (ECG) \[including QTcF less than or equal to (\<=) 450 millisecond (msec)\] performed at screening, admission to the clinical unit and pre dose on Day 1 of Period 1. Abnormalities, which are not considered to be of clinical significance by the investigator, are acceptable. The presence of Left Bundle Branch Block (LBBB), AV Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator \[ICD\] will lead to exclusion * Non-smoker (not smoked for 3 months prior to screening) * During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, in addition to the highly effective method of contraception, a man who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (for example, condom with spermicidal foam/gel/film/cream/suppository); who is sexually active with a woman who is pregnant must use a condom; must agree not to donate sperm Exclusion Criteria: * History of or current significant medical illness including (but not limited to psychotic, bipolar, major depressive, or anxiety disorder) * Cardiac arrhythmias or other cardiac disease, hematological disease, lipid abnormalities, respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, Parkinson's disease, infection, or any other illness that the Investigator considers should exclude the participant * Serology positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies * Participant has a history of or current vestibular disease including (but not limited to) Meniere's disease, benign paroxysmal positional vertigo (BPPV), vestibular neuronitis, vestibular schwannoma or vestibular migraine * Only for part 2: Has a current diagnosis or history of narcolepsy, central sleep apnea, sleep related hypoventilation, circadian rhythm sleep-wake disorders, substance/medication induced sleep disorder or parasomnias (non-rapid eye movement sleep arousal disorders, nightmare disorder, rapid eye movement sleep behavior disorder); obstructive sleep apnea/hypopnea (apnea/hypopnea index greater than (\>)10) or restless legs syndrome (periodic leg movements with arousal index \>15); night-shift worker or significantly shifted diurnal activity pattern (it is expected that eligible participant normally wake up between 6:00 am - 8:00 am and go to bed between 10:00 pm - 12:00 am); usual bedtime outside of 10:00 pm and 12:00 am and taking, on average, less than 6 hours or more than 9 hours of bed rest

Locations (1)

PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini

Groningen, Netherlands

Outcomes

Primary Outcomes

Part 1 (Day-Time Dosing): Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

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

Time frame: Up to Week 8

Part 2 (Night-Time Dosing): Number of Participants with AEs as a Measure of Safety and Tolerability

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

Time frame: Up to Week 9

Secondary Outcomes

Slow Wave Activity Recorded by the Electroencephalogram (EEG)

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.

Time frame: Pre-dose, 1 hour (h), 2h, and 4h post dose on Day 1

Part 1: PD of JNJ-55375515 as Assessed by Heart Rate Variability (HRV)

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Participants will receive JNJ-55375515 orally at a Dose level 4 in Part 1 of study.

JNJ-55375515 Dose Level 5DRUG

Participants will receive JNJ-55375515 orally at a Dose level 5 in Part 1 of study.

JNJ-55375515 Dose Level 6DRUG

Participants will receive JNJ-55375515 orally at a Dose level 6 in Part 1 of study.

PlaceboDRUG

All participants will receive matching placebo orally in Part 1 and Part 2 of the study.

JNJ-55375515DRUG

Participants will receive JNJ-55375515 as per the assigned treatment in Part 2.

Time frame: Pre-dose (Day 1) up to 24 hours post dose

Part 1: Saccadic Reaction Time (RT) as Measured by Saccadic Eye Movements

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.

Time frame: Pre-dose, 1 h, 2h, and 4h post dose on Day 1

Part 1: Saccadic Peak Velocity (SPV) as Measured by Saccadic Eye Movements

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.

Time frame: Pre-dose, 1h, 2h, and 4h post dose on Day 1

Part 1: Change from Baseline in Body Sway

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.

Time frame: Baseline, 1h, 2h, and 4h post dose on Day 1

Part 1 and 2: PD as Assessed by Karolinska Sleepiness Scale (KSS) Score

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).

Time frame: Part 1: Pre-dose, 1h, 3h, and 8h post dose on Day 1; Part 2: Pre-dose (Day 1) and 8h post dose (Day 2)

Part 1: Change from Baseline in Bond and Lader Visual Analogue Scale (B&L VAS) Score

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.

Time frame: Baseline, 1h, 2h, and 4h post dose on Day 1

Part 1 and 2: Change from Baseline in Cortisol Levels

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.

Time frame: Part 1: Baseline, 0.5h, 1h, 2h, 3h, 4h, 5h 45minutes (m), 6h, 6h 05m, 6h 25m, 6h 30m, 6h 50m, 6h 55m, 7h 15m, 7h 35m, 8h, 12h and 24h post dose on Day 1; Part 2: Baseline, 0.5h, 1h, 2h (Day 1 or 2), 3h, 4h, 6h, 8h, 12h and 24h post dose on Day 2

Part 1: PD as Assessed by Probabilistic Instrumental Learning Task (PILT)

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.