Clinical trial NCT03405441: A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-55375515 in Healthy Male Participants
Official title: A 2-Part, Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-55375515 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 42
Sex: MALE
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1 (Day-Time Dosing): Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to Week 8
measure: Part 2 (Night-Time Dosing): Number of Participants with AEs as a Measure of Safety and Tolerability
timeFrame: Up to Week 9
Secondary outcomes:
measure: Slow Wave Activity Recorded by the Electroencephalogram (EEG)
timeFrame: Pre-dose, 1 hour (h), 2h, and 4h post dose on Day 1
measure: Part 1: PD of JNJ-55375515 as Assessed by Heart Rate Variability (HRV)
timeFrame: Pre-dose (Day 1) up to 24 hours post dose
measure: Part 1: Saccadic Reaction Time (RT) as Measured by Saccadic Eye Movements
timeFrame: Pre-dose, 1 h, 2h, and 4h post dose on Day 1
measure: Part 1: Saccadic Peak Velocity (SPV) as Measured by Saccadic Eye Movements
timeFrame: Pre-dose, 1h, 2h, and 4h post dose on Day 1
measure: Part 1: Change from Baseline in Body Sway
timeFrame: Baseline, 1h, 2h, and 4h post dose on Day 1
measure: Part 1 and 2: PD as Assessed by Karolinska Sleepiness Scale (KSS) Score
timeFrame: 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)
measure: Part 1: Change from Baseline in Bond and Lader Visual Analogue Scale (B&L VAS) Score
timeFrame: Baseline, 1h, 2h, and 4h post dose on Day 1
measure: Part 1 and 2: Change from Baseline in Cortisol Levels
timeFrame: 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
measure: Part 1: PD as Assessed by Probabilistic Instrumental Learning Task (PILT)
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: International Shopping List Test
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: Groton Maze Learning Task
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: Social Emotional Cognition Task
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: Detection Task
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: Identification Task
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: one Back Task
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: International Shopping List Test - Delayed Recall
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: PD as Assessed by Cognitive Test Battery: Groton Maze Learning - Delayed Recall
timeFrame: Pre-dose, 3h, and 8h post dose on Day 1
measure: Part 1: Evoked Stress Response as Assessed by Induced Stress
timeFrame: 6h 30m to 6h 50m post dose on Day 1
measure: Part 2: Latency to Persistent Sleep (LPS) by 8-hour Overnight Polysomnography
timeFrame: 0 hour (Day 1) up to 8 Hour (Day 2)
measure: Part 2: Total Time Spent in Deep Sleep (Duration of Slow Wave Sleep) - Stage 3 Sleep by 8-Hour Overnight Polysomnography
timeFrame: 0 hour (Day 1) up to 8 Hour (Day 2)
measure: Part 2: Time in bed by 8-hour Overnight Polysomnography
timeFrame: 0 hour (Day 1) up to 8 Hour (Day 2)
measure: Part 2: Cognitive Test Battery: Continuous Paired Associate Learning Task (CPAL)
timeFrame: -7 hour (Day 1), 17 hour (Day 2)
measure: Part 1 and 2: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Part 1: Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, and 96h post dose; Part 2: Pre dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 46h, 70h, and 94h post dose
measure: Part 1 and 2: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Part 1: Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, and 96h post dose; Part 2: Pre dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 46h, 70h, and 94h post dose
measure: Part 1 and 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentrations (AUC[0-last])
timeFrame: Part 1: Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, and 96h post dose; Part 2: Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 46h, 70h, and 94h post dose
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: