A Study to Evaluate the Pharmacokinetics of Guselkumab and Ustekinumab Following a Single Intravenous or Subcutaneous Administration in Healthy Chinese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Maximum Observed Serum Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics (PK) of guselkumab following a single intravenous (IV) or subcutaneous (SC) administration in healthy Chinese participants; to evaluate the PK of ustekinumab following a single IV administration in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 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
- •Participants must be healthy with no clinically significant abnormalities as determined by medical history, physical examination, blood chemistry assessments, hematologic assessments, urinalysis, measurement of vital signs, and electrocardiogram (ECG)
- •A woman must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and Day-1
- •Must agree to use an adequate contraception method as deemed appropriate by the investigator; to always use a condom during intercourse and to not donate sperm during the study and for 16 weeks after study drug administration
- •Must be a nonsmoker or agree to smoke no more than 10 cigarettes or 2 cigars per day throughout the study. However, during the inpatient portion of the study if smoking is not allowed in the inpatient unit, smokers will not be allowed to smoke cannot use nicotine replacement products
- •Must agree to abstain from alcohol intake 48 hours before study drug administration and during the inpatient period of the study. After this time, participants must not consume more than 10 grams of alcohol (e.g. 250 milliliter (mL) beer with 5 percent (%) alcohol content) per day for the duration of the study
排除标准
- •History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, gastro-intestinal disease, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- •Has had major surgery, (for example, requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study
- •Has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients
- •Has received an experimental antibody or biologic therapy within the previous 6 months
- •Has a history of, or ongoing, chronic, or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection
研究组 & 干预措施
Cohort 5: Ustekinumab (IV): 6 mg/mL
Participants will receive a single IV infusion of ustekinumab 6 milligrams per milliliter (mg/mL) solution on Day 1.
干预措施: Ustekinumab 6 mg/mL (Drug)
结局指标
主要结局
Maximum Observed Serum Concentration (Cmax)
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
The Cmax is the maximum observed serum concentration.
Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
AUC (0-infinity) is the area under the serum concentration versus time curve from time zero to infinity with extrapolation of the terminal phase.
Area Under Serum Concentration From Time Zero to the Last Quantifiable Concentration (AUC [0-last])
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
AUC (0-last) area under the serum concentration versus time curve from time zero to the time corresponding to the last quantifiable concentration.
Elimination Half-Life (T1/2)
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
Elimination half-life is time measured for the serum 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).
Total Systemic Clearance (CL)
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose is estimated by dividing the total administered dose by the serum area under the serum concentration-time curve from time zero to infinite time (AUC \[0-infinity\]).
Volume of Distribution (Vz)
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
The Vz is total volume of distribution at terminal phase after intravenous (IV) administration, defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time to Reach Maximum Observed Serum Concentration (Tmax)
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
Tmax is time correspondent to the maximum observed serum concentration.
Apparent Total Systemic Clearance (CL/F)
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
Apparent total systemic clearance is clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Volume of Distribution (Vz/F)
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after subcutaneous dose (Vz/F) is influenced by the fraction absorbed.
Absolute Bioavailability (F [%])
时间窗: Predose (Day 1), 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours postdose (Day 7); Days 15, 22, 29, 43, 57, 71, and 85
Absolute bioavailability is the percentage of the orally administered dose that is systemically available. It is calculated as (AUC \[0-infinity\] for test)/(AUC \[0-infinity\] for reference \[ref\])\*(D for ref/D for test)\*100, where the reference treatment is an intravenous administration, AUC (0-infinity) is area under the concentration-time curve from time zero to extrapolated infinite time, and D is the dose of administered drug.
次要结局
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Up to Week 16)
- Number of Participants with Anti-Guselkumab and Anti-Ustekinumab Antibodies(Predose (Day 1) and on Days 15, 29, 57, and 85)