A Double-blind, Placebo-controlled, Randomized, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-64264681 in Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- SAD: Apparent Elimination Half-life (t1/2)
研究概览
简要总结
The primary purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of JNJ-64264681 in healthy participants after single and multiple oral doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 58 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must have a body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2) (BMI = weight[kg]/height[m]^2), and a body weight of not less than 50 kilogram (kg)
- •Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead Electrocardiogram (ECG) performed at screening and Day -1
- •Participant must be healthy on the basis of clinical laboratory tests performed at screening and Day -
- •If the results of the serum chemistry panel, coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- •Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
- •Female participants must not be of childbearing potential by fulfilling 1 of the criteria below: a) Be over 45 years of age with no menses for 12 months without an alternative medical cause, with screening follicle stimulating hormone (FSH) levels of greater than (>)40 International Units Per Liter (IU/L) or milli-international units per milliliter (mIU/mL). b) Be permanently surgically sterile. Permanent surgical sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy. Documentation of FSH levels is not required in the case of surgical sterility
排除标准
- •Participant has current, or history of clinically significant medical illness including, but not limited to, liver or renal insufficiency, significant cardiac (including heart valve disease), vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- •Participant has a history of abnormal bleeding or bruising
- •Participant has a history of atrial fibrillation or history of arrhythmias
- •Participant has history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)
- •Participant has known allergies, hypersensitivity, or intolerance to polyethylene glycol 400 (PEG400) (vehicle for JNJ-64264681 for oral solution dosing) for participant in a cohort where study drug is to be dosed as an oral solution, or to microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, silica dioxide, sodium lauryl sulfate, magnesium stearate, or gelatin (excipients in the solid dose formulation (capsule) of JNJ-64264681) for participant in a solid dose formulation cohort
研究组 & 干预措施
Multiple Ascending Dose (MAD)
The MAD part will consist of 3 dose escalation cohorts of males and females. Participants will receive once-daily oral doses of JNJ-64264681 or placebo for 10 consecutive days.
干预措施: JNJ-64264681 (Drug)
Single Ascending Dose (SAD)
The SAD part will consist of 6 escalating dose cohorts and 1 fed cohort of healthy male participants, 2 dose escalating cohorts of healthy female participants, and 1 solid dose formulation (capsule) cohort of healthy male participants, who will be dosed after completion of the dose escalation cohorts. Participants in each cohort (except for the solid dose formulation cohort) will receive JNJ-64264681 or Placebo on Day 1, orally. In the solid dose formulation cohort, participants will receive JNJ-64264681 capsule on Day 1. Doses for the female cohorts and fed cohort will be selected based on safety, tolerability, pharmacokinetics (PK),and pharmacodynamic (PD) data from preceding cohorts and the dose for the solid dose formulation cohort will be selected and approximately equal to a dose previously studied in the single ascending dose cohorts.
干预措施: JNJ-64264681 (Drug)
Single Ascending Dose (SAD)
The SAD part will consist of 6 escalating dose cohorts and 1 fed cohort of healthy male participants, 2 dose escalating cohorts of healthy female participants, and 1 solid dose formulation (capsule) cohort of healthy male participants, who will be dosed after completion of the dose escalation cohorts. Participants in each cohort (except for the solid dose formulation cohort) will receive JNJ-64264681 or Placebo on Day 1, orally. In the solid dose formulation cohort, participants will receive JNJ-64264681 capsule on Day 1. Doses for the female cohorts and fed cohort will be selected based on safety, tolerability, pharmacokinetics (PK),and pharmacodynamic (PD) data from preceding cohorts and the dose for the solid dose formulation cohort will be selected and approximately equal to a dose previously studied in the single ascending dose cohorts.
干预措施: Placebo (Drug)
Multiple Ascending Dose (MAD)
The MAD part will consist of 3 dose escalation cohorts of males and females. Participants will receive once-daily oral doses of JNJ-64264681 or placebo for 10 consecutive days.
干预措施: Placebo (Drug)
结局指标
主要结局
SAD: Apparent Elimination Half-life (t1/2)
时间窗: Up to Day 3
t1/2 is apparent elimination half-life of JNJ-64264681 associated with the terminal slope (z) of the semi-logarithmic drug concentration-time curve.
SAD: Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: Up to Day 4
Tmax is defined as actual sampling time to reach maximum observed concentration.
MAD: Maximum Observed Plasma Concentration (Cmax)
时间窗: Up to Day 13
Cmax is the maximum observed plasma JNJ-64264681 concentration.
MAD: Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: Up to Day 13
Tmax is defined as actual sampling time to reach maximum observed concentration.
MAD: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24])
时间窗: Day 1: Up to 24 hours post-dose
AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.
SAD: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUClast)
时间窗: Up to Day 4
AUClast is defined as area under the plasma JNJ-64264681 concentration-time curve from time 0 to time of the last observed quantifiable concentration.
MAD: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
时间窗: Day 10
AUCtau is area under the plasma JNJ-64264681 concentration-time curve during a dosing interval (tau) at steady-state.
SAD: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
时间窗: Up to Day 3
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(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
MAD: Apparent Elimination Half-life (t1/2)
时间窗: Up to Day 13
t1/2 is apparent elimination half-life of JNJ-64264681 associated with the terminal slope (z) of the semi-logarithmic drug concentration-time curve.
MAD: Accumulation Ratio
时间窗: Up to Day 13
MAD: Accumulation Ratio obtained by dividing AUC of JNJ-64264681 at two different time points.
Single Ascending Dose (SAD): Number of Participants with Adverse Events
时间窗: Up to Day 14
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
SAD: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24])
时间窗: Day 1: Up to 24 hours post-dose
AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.
Multiple Ascending Dose (MAD): Number of Participants with Adverse Events
时间窗: Up to Day 24
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
SAD: Maximum Observed Plasma Concentration (Cmax)
时间窗: Up to Day 4
Cmax is the maximum observed plasma JNJ-64264681 concentration.
SAD: Time to Last Quantifiable Plasma Concentration (Tlast)
时间窗: Up to Day 4
The Tlast is the time to last observed quantifiable plasma concentration.
MAD: Time to Last Quantifiable Plasma Concentration (Tlast)
时间窗: Up to Day 13
The Tlast is the time to last observed quantifiable plasma concentration.
次要结局
未报告次要终点