A Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-61393215 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 主要终点
- Time of the Last Quantifiable Plasma Concentration (Tlast) of JNJ-61393125
研究概览
简要总结
The purpose of this study is to investigate the safety and tolerability of JNJ-61393215 versus placebo after single oral dose administration under fasted (ascending dose levels) and fed condition, to characterize the pharmacokinetics of JNJ-61393125 in plasma, cerebrospinal fluid (CSF) and urine after single oral dose administration and to investigate the effect of food (high fat/high calorie) on the pharmacokinetics of JNJ-61393215 following single oral dose administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must have a body mass index (BMI) between 18 and 30 kilogram per meter square kg/m^2, inclusive (BMI = weight/height^2)
- •Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening and admission to the clinical unit. Minor abnormalities in ECG, which are not considered to be of clinical significance by the investigator, are acceptable. The presence of Left Bundle Branch Block (LBBB), Atrioventricular (AV) Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator [ICD] will lead to exclusion
- •Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant
- •A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control example, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository during the study and for 3 months after receiving the last dose of study drug. All men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partner should also use an appropriate method of birth control for at least the same duration.
- •Healthy male participants between 18 and 54 years of age, inclusive for Part 1 and 3
- •Healthy male and female participants between 55 and 75 years of age, inclusive in Part 2
排除标准
- •Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness. Minor deviations, which are not considered to be of clinical significance to both the investigator and to the Janssen Safety Responsible Physician, are acceptable
- •Participant has estimated glomerular filtration rate (eGFR) less than (<) 60 milliliters per minute per 1.73 meter square (mL/min/1.73m^2) at Screening
- •Participant has a heart rate less than (<) 50 beats per minute (bpm) at Screening or at admission to the clinical unit
- •Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
- •Participant has Left Bundle Branch Block (LBBB), Atrioventricular (AV) Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator [ICD]
研究组 & 干预措施
Part 1: Cohort 2
Participants will receive 5 mg JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 4
Participants will receive 30 mg JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 1: Cohort 1
Participants will receive 1 milligram (mg) JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 1
Participants will receive 1 milligram (mg) JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 1: Cohort 2
Participants will receive 5 mg JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 1: Cohort 3
Participants will receive 15 mg JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 3
Participants will receive 15 mg JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 1: Cohort 4
Participants will receive 30 mg JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 5
Participants will receive 45 mg JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 5
Participants will receive 45 mg JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 1: Cohort 6
Participants will receive 60 mg JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 6
Participants will receive 60 mg JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 1: Cohort 7
Participants will receive 90 mg JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 7
Participants will receive 90 mg JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 1: Cohort 8
Participants will receive 120 mg JNJ-61393215 or placebo.
干预措施: JNJ-61393215 (Drug)
Part 1: Cohort 8
Participants will receive 120 mg JNJ-61393215 or placebo.
干预措施: Placebo (Drug)
Part 2
Participants will receive JNJ-61393215 (dose to be determined).
干预措施: JNJ-61393215 (Drug)
Part 3
Participants will receive JNJ-61393125 (dose to be determined) or placebo under fed conditions.
干预措施: JNJ-61393215 (Drug)
Part 3
Participants will receive JNJ-61393125 (dose to be determined) or placebo under fed conditions.
干预措施: Placebo (Drug)
结局指标
主要结局
Time of the Last Quantifiable Plasma Concentration (Tlast) of JNJ-61393125
时间窗: Up to Day 4
The Tlast is defined as the time of the last quantifiable plasma concentration.
Creatinine Clearance (CLcr) of JNJ-61393125
时间窗: Up to Day 4
Number of Participants With Adverse Events and Serious Adverse Events as a Measure of Safety and Tolerability
时间窗: Up to follow-up phase (7 to 14 days after study drug administration)
First Order Rate Constant (Lambda[z]) of JNJ-61393125
时间窗: Up to Day 4
Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Maximum Plasma Concentration (Cmax) of JNJ-61393125
时间窗: Up to Day 4
The Cmax is the maximum observed plasma concentration.
Time to Reach Maximum Plasma Concentration (Tmax) of JNJ-61393125
时间窗: Up to Day 4
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Elimination Half-life (t1/2) of JNJ-61393125
时间窗: Up to Day 4
Elimination half-life (t \[1/2\]) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
Last Quantifiable Plasma Concentration (Clast) of JNJ-61393125
时间窗: Up to Day 4
The Clast is the last quantifiable plasma concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration of JNJ-61393125
时间窗: Up to Day 4
The (AUC \[0-last\]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.
Total Clearance (CL/F) of JNJ-61393125
时间窗: Up to Day 4
Total clearance of drug after extravascular administration, uncorrected for absolute bioavailability, calculated as: D/AUC infinity.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-61393125
时间窗: Up to Day 4
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
次要结局
- Change From Baseline in NeuroCart test battery Score(Up to Day 2)
- Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT Fatigue)(Up to Day 2)
- Visual Verbal Learning Test (VVLT) Score(Up to Day 2)