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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Part 2 (Night-Time Dosing): Number of Participants with AEs as a Measure of Safety and Tolerability
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 54 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
- •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
排除标准
- •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
研究组 & 干预措施
Part 1 (Panel 1): JNJ-55375515 and placebo
Participants will receive dose level (DL) 1 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 3 (period 2) and a maximum of DL 5 (period 3) based on the safety and tolerability profile and pharmacodynamic (PD) profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: JNJ-55375515 Dose Level 1 (Drug)
Part 1 (Panel 1): JNJ-55375515 and placebo
Participants will receive dose level (DL) 1 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 3 (period 2) and a maximum of DL 5 (period 3) based on the safety and tolerability profile and pharmacodynamic (PD) profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: JNJ-55375515 Dose Level 3 (Drug)
Part 1 (Panel 1): JNJ-55375515 and placebo
Participants will receive dose level (DL) 1 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 3 (period 2) and a maximum of DL 5 (period 3) based on the safety and tolerability profile and pharmacodynamic (PD) profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: JNJ-55375515 Dose Level 5 (Drug)
Part 1 (Panel 1): JNJ-55375515 and placebo
Participants will receive dose level (DL) 1 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 3 (period 2) and a maximum of DL 5 (period 3) based on the safety and tolerability profile and pharmacodynamic (PD) profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: Placebo (Drug)
Part 1 (Panel 2): JNJ-55375515 and placebo
Participants will receive DL 2 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 4 (period 2) and a maximum of DL 6 (period 3) based on the safety and tolerability profile and PD profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: JNJ-55375515 Dose Level 2 (Drug)
Part 1 (Panel 2): JNJ-55375515 and placebo
Participants will receive DL 2 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 4 (period 2) and a maximum of DL 6 (period 3) based on the safety and tolerability profile and PD profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: JNJ-55375515 Dose Level 4 (Drug)
Part 1 (Panel 2): JNJ-55375515 and placebo
Participants will receive DL 2 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 4 (period 2) and a maximum of DL 6 (period 3) based on the safety and tolerability profile and PD profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: JNJ-55375515 Dose Level 6 (Drug)
Part 1 (Panel 2): JNJ-55375515 and placebo
Participants will receive DL 2 of JNJ-55375515 (starting dose) or placebo on Day 1 of period 1 based on their randomization sequence 1, 2 or 3. Dose of the study medication will be escalated to DL 4 (period 2) and a maximum of DL 6 (period 3) based on the safety and tolerability profile and PD profile assessed at the preceding dose level. A wash-out period of at least 10 days will be maintained between study drug administrations.
干预措施: Placebo (Drug)
Part 2: JNJ-55375515 and placebo
Participants will randomly be assigned to one of four treatment sequences 1, 2, 3 or 4. In the first 3 sequences, participants will receive 2 doses of JNJ-55375515 and placebo. Participants assigned to sequence 4 will receive placebo only in all periods. 3 dose levels will be tested in Part 2 based on Part 1 and will not exceed those evaluated in Part 1. A wash-out period of at least 10 days will be maintained between study drug administrations in period 1, 2, 3 and 4. In period 4 (open-label pharmacokinetic (PK) assessment period) participants will be randomly assigned to one of two dose levels tested in periods 1 to 3.
干预措施: Placebo (Drug)
Part 2: JNJ-55375515 and placebo
Participants will randomly be assigned to one of four treatment sequences 1, 2, 3 or 4. In the first 3 sequences, participants will receive 2 doses of JNJ-55375515 and placebo. Participants assigned to sequence 4 will receive placebo only in all periods. 3 dose levels will be tested in Part 2 based on Part 1 and will not exceed those evaluated in Part 1. A wash-out period of at least 10 days will be maintained between study drug administrations in period 1, 2, 3 and 4. In period 4 (open-label pharmacokinetic (PK) assessment period) participants will be randomly assigned to one of two dose levels tested in periods 1 to 3.
干预措施: JNJ-55375515 (Drug)
结局指标
主要结局
Part 2 (Night-Time Dosing): Number of Participants with AEs as a Measure of Safety and Tolerability
时间窗: Up to Week 9
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Part 1 (Day-Time Dosing): Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
时间窗: Up to Week 8
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
次要结局
- Slow Wave Activity Recorded by the Electroencephalogram (EEG)(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)(Pre-dose (Day 1) up to 24 hours post dose)
- Part 1: Saccadic Reaction Time (RT) as Measured by Saccadic Eye Movements(Pre-dose, 1 h, 2h, and 4h post dose on Day 1)
- Part 1: Saccadic Peak Velocity (SPV) as Measured by Saccadic Eye Movements(Pre-dose, 1h, 2h, and 4h post dose on Day 1)
- Part 1: Change from Baseline in Body Sway(Baseline, 1h, 2h, and 4h post dose on Day 1)
- Part 1 and 2: PD as Assessed by Karolinska Sleepiness Scale (KSS) Score(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(Baseline, 1h, 2h, and 4h post dose on Day 1)
- Part 2: Total Time Spent in Deep Sleep (Duration of Slow Wave Sleep) - Stage 3 Sleep by 8-Hour Overnight Polysomnography(0 hour (Day 1) up to 8 Hour (Day 2))
- Part 1 and 2: Change from Baseline in Cortisol Levels(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)(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: International Shopping List Test(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: Groton Maze Learning Task(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: Social Emotional Cognition Task(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: Detection Task(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: Identification Task(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: one Back Task(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: International Shopping List Test - Delayed Recall(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: PD as Assessed by Cognitive Test Battery: Groton Maze Learning - Delayed Recall(Pre-dose, 3h, and 8h post dose on Day 1)
- Part 1: Evoked Stress Response as Assessed by Induced Stress(6h 30m to 6h 50m post dose on Day 1)
- Part 2: Latency to Persistent Sleep (LPS) by 8-hour Overnight Polysomnography(0 hour (Day 1) up to 8 Hour (Day 2))
- Part 2: Time in bed by 8-hour Overnight Polysomnography(0 hour (Day 1) up to 8 Hour (Day 2))
- Part 2: Cognitive Test Battery: Continuous Paired Associate Learning Task (CPAL)(-7 hour (Day 1), 17 hour (Day 2))
- Part 1 and 2: Maximum Observed Plasma Concentration (Cmax)(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)
- Part 1 and 2: Time to Reach Maximum Observed Plasma Concentration (Tmax)(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)
- Part 1 and 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentrations (AUC[0-last])(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)