A Phase 1, Open-label Single-dose Crossover, and Double-blind Multiple-dose Parallel Group Study to Characterize the Pharmacokinetics, Safety and Tolerability, and Pharmacodynamics of JNJ-70033093 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Part 1: Maximum Observed Analyte Concentration (Cmax) of JNJ-70033093
研究概览
简要总结
The purpose of this study is to characterize the pharmacokinetic (PK) of multiple twice-daily doses of JNJ-70033093 in healthy participants and to assess the effects of dosing time and food on the PK of single-dose of JNJ-70033093 in healthy 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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy on the basis of medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory test results, including serum chemistry, blood coagulation, hematology, and urinalysis performed at screening. If there are abnormalities, the investigator may decide that the abnormalities or deviations from normal are not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- •If a woman, except for postmenopausal women, must have a negative highly sensitive serum (beta human chorionic gonadotropin [beta-hCG]) at screening and urine (beta-hCG) pregnancy test on Day -1 of treatment period
- •Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
- •Body mass index (BMI; weight kilogram per meter square [kg/m^2]) between 18 and 30 kg/m^2 (inclusive), and body weight not less than 50 kilogram (kg)
- •After being supine for 10 minutes, systolic blood pressure between 90 and 140 millimeter of Mercury (mmHg), inclusive; and no higher than 90 mmHg diastolic blood pressure
排除标准
- •If a woman, pregnant, breast-feeding or planning to become pregnant during the study
- •History of any known illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant or that could prevent, limit or confound the protocol specified assessments. This may include but is not limited to any known bleeding or clotting disorder, a history of arterial or venous thrombosis, liver or renal dysfunction, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic abnormalities, metabolic disturbances, or poor venous access
- •Participants with current hepatitis B infection (confirmed by hepatitis B surface antigen [HBsAg]), or hepatitis C infection (confirmed by hepatitis C virus [HCV] antibody), or human immunodeficiency virus type-1 (HIV-1) or HIV-2 infection at study screening
- •History of, or a reason to believe a participant has a history of, drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM V) criteria within the past 1 year, which in the investigator's opinion would compromise participant safety and/or compliance with the study procedures
- •History of any clinically significant drug or food allergies (such as anaphylaxis or hepatotoxicity) and known allergy to the study drugs or any of the excipients of the formulation. History of allergy to or unwillingness to consume any component of the high-fat breakfast menu to be provided in this study
- •Clinically significant abnormal values for hematology, coagulation, clinical chemistry or urinalysis at Screening or on Day -1 prior to the first dosing as determined by the investigator or appropriate designee. Any of the following laboratory results outside of the ranges specified below at screening or Day -1 prior to first dosing, confirmed by repeat: Hemoglobin or hematocrit < lower limit of normal; Platelet count < lower limit of normal; activated partial thromboplastin time (aPTT), or prothrombin time (PT) greater than (>) 1.2 × upper limit of normal (ULN)
- •Any of the following on 12-lead ECG and assessment of QT interval prior to study treatment administration, confirmed by repeat at screening and Day -1 of treatment period: Heart rate >100 beats per minute (bpm); PR >= 210 milli second (ms); QRS >=120 ms; QTcF >= 450 ms for male and >= 470 ms for female
研究组 & 干预措施
Part 1: Treatment C
Participants will receive JNJ-70033093 dose BID for 8 days followed by a JNJ-70033093 dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: JNJ-70033093 (Drug)
Part 1: Treatment A
Participants will receive JNJ-70033093 dose twice daily (BID) for 8 days followed by a placebo dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: JNJ-70033093 (Drug)
Part 1: Treatment A
Participants will receive JNJ-70033093 dose twice daily (BID) for 8 days followed by a placebo dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: Placebo (Drug)
Part 1: Treatment B
Participants will receive JNJ-70033093 dose BID for 8 days followed by a placebo dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: JNJ-70033093 (Drug)
Part 1: Treatment B
Participants will receive JNJ-70033093 dose BID for 8 days followed by a placebo dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: Placebo (Drug)
Part 1: Treatment C
Participants will receive JNJ-70033093 dose BID for 8 days followed by a JNJ-70033093 dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: Placebo (Drug)
Part 1: Treatment D
Participants will receive JNJ-70033093 dose BID for 8 days followed by a JNJ-70033093 dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: JNJ-70033093 (Drug)
Part 1: Treatment D
Participants will receive JNJ-70033093 dose BID for 8 days followed by a JNJ-70033093 dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9.
干预措施: Placebo (Drug)
Part 2: Treatment Sequence EFG
Participants will receive Treatment E (JNJ-7003309 single dose in the morning in fasted condition) in treatment Period 1; followed by Treatment F (JNJ-7003309 single dose administered in the evening in fasted condition) in treatment Period 2; followed by Treatment G (JNJ-7003309 single dose administered in the evening in fasted condition) in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period.
干预措施: JNJ-70033093 (Drug)
Part 2: Treatment Sequence FGE
Participants will receive Treatment F in treatment Period 1; followed by Treatment G in treatment Period 2; followed by Treatment E in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period.
干预措施: JNJ-70033093 (Drug)
Part 2: Treatment Sequence GEF
Participants will receive Treatment G in treatment Period 1; followed by Treatment E in treatment Period 2; followed by Treatment F in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period
干预措施: JNJ-70033093 (Drug)
Part 2: Treatment Sequence EGF
Participants will receive Treatment E in treatment Period 1; followed by Treatment G in treatment Period 2; followed by Treatment F in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period
干预措施: JNJ-70033093 (Drug)
Part 2: Treatment Sequence GFE
Participants will receive Treatment G in treatment Period 1; followed by Treatment F in treatment Period 2; followed by Treatment E in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period
干预措施: JNJ-70033093 (Drug)
Part 2: Treatment Sequence FEG
Participants will receive Treatment F in treatment Period 1; followed by Treatment E in treatment Period 2; followed by Treatment G in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period
干预措施: JNJ-70033093 (Drug)
结局指标
主要结局
Part 1: Maximum Observed Analyte Concentration (Cmax) of JNJ-70033093
时间窗: Up to Day 9
Cmax is the maximum observed analyte concentration.
Part 1: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of JNJ-70033093
时间窗: Up to Day 9
Tmax is the actual sampling time to reach the maximum observed analyte concentration
Part 2: Maximum Observed Analyte Concentration (Cmax) of JNJ-70033093
时间窗: Up to Day 9
Cmax is the maximum observed analyte concentration.
Part 2: Area Under the Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUC [0-last]) of JNJ-70033093
时间窗: Up to Day 9
AUC (0-last) is area under the analyte concentration-time curve (AUC) from time 0 to time of the last quantifiable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Part 1: Area Under the Analyte Concentration-time Curve from Time Zero to 12 Hours (AUC[0-12h]) of JNJ-70033093
时间窗: 12 hours postdose (Day 1)
AUC(0-12h) is the area under the time-concentration curve (AUC) from time 0 (dosing time) to 12 hours before steady state.
Part 1: Apparent Terminal Elimination Half-life (t[1/2]) of JNJ-70033093
时间窗: Up to Day 9
T(1/2) is the apparent terminal elimination half-life is the time measured for the analyte concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Part 2: Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of JNJ-70033093
时间窗: Up to Day 9
AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.
次要结局
- Percentage Change from Baseline in Activated Partial Thromboplastin Time (aPTT)(Baseline up to Day 9 (Part 1); Baseline up to Day 11 (Part 2))
- Percentage Change from Baseline in Factor XI Clotting Activity(Baseline up to Day 9 (Part 1); Baseline up to Day 11 (Part 2))
- Number of Participants with Vital Sign Abnormalities(Up to 51 days)
- Number of Participants with Abnormal Electrocardiogram (ECG) Findings(Up to 51 days)
- Number of Participants with Abnormal Laboratory Findings(Up to 51 days)
- Relationship Between JNJ-70033093 Plasma Concentrations and QTc After Multiple Doses of JNJ-70033093(Up to Day 9)
- Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability(Up to 51 days)