Pharmacokinetic Study of E7080/Lenvatinib in Chinese Subjects With Solid Tumor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Area under the concentration-time curve over the dosing interval on multiple dosing (AUC[0-τ])
研究概览
简要总结
Study E7080-C086-108 is an open-label, single- and multiple-dose pharmacokinetic (PK) study of lenvatinib (administered orally, once a day [QD]) in Chinese participants with solid tumor. A total of 12 participants will be enrolled to evaluate the PK of 24 milligrams (mg) QD dosing of lenvatinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a histological and/or cytological diagnosis of solid tumor
- •Participants with solid tumor that is resistant to standard anti-tumor therapies, or for which no appropriate treatment is available
- •Participants whose toxicity of previous treatment has recovered to Grade 1 or lower (except for alopecia)
- •Participants who have completed previous anti-tumor therapy (such as surgery, radiotherapy) at least 4 weeks before treatment
- •Participants who are 18 years or older at the time of obtaining informed consent
- •Participants with an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
- •Participants who meet all of the following items:
- •Hemoglobin ≥9.0 grams per deciliter (g/dL)
- •Neutrophil count ≥1.5×10^3/microliters (µL)
- •Platelet count ≥10×10^4/µL
- •Total bilirubin ≤1.8 milligrams (mg)/dL
- •Aspartate aminotransferase (AST) ≤100 International Units per liter (IU/L)
- •Alanine aminotransferase (ALT) ≤100 IU/L
- •Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥50 milliliters per minute (mL/min). Creatinine clearance will be calculated based on Cockcroft-Gault method using the following formula: Male: (140-age) × weight ÷ (serum creatinine × 72); Female: 0.85 × (140-age) × weight ÷ (serum creatinine × 72).
- •Participants expected to survive for 12 weeks or longer
- •Males and females of childbearing potential must agree to use appropriate contraception from the giving of consent to 30 days after study drug administration. Female participants of childbearing potential must test negative for pregnancy at screening
- •Participants who voluntarily agree to participate in this study in writing
排除标准
- •Participants with brain metastasis accompanied by clinical symptoms or requiring treatment
- •Participants with the following complications or medical history
- •Systemic severe infections requiring medical treatment
- •The following cardiovascular diseases
- •Ischemic cardiac disease or arrhythmia requiring medical treatment
- •Angina pectoris or myocardial infarction within 24 weeks before enrollment
- •Corrected QT interval (QTc) greater than 480 milliseconds (msec) (Fridericia's method)
- •Hemoptysis (fresh blood) ≥ 1/2 teaspoon (2.5 mL) or clinically significant hemorrhagic or thrombotic events within 4 weeks before enrollment
- •Systolic pressure ≥150 millimeters of mercury (mmHg) and diastolic pressure ≥90 mmHg
- •If proteinuria is ≥2+ in a qualitative test for urine protein, ≥1.0 grams for 24 hours is accumulated
- •Complications or surgery (such as malabsorption syndrome, chronic diarrhea, or total gastrectomy) that could significantly influence the absorption of the investigational drug
- •Have undergone major surgery within 4 weeks before enrollment
- •Co-existing effusion requiring treatment
- •Participants unable to take oral medication
- •Participants scheduled for surgery during the projected course of the study
- •Participants who test positive for human immunodeficiency virus (HIV antibody), or positive for hepatitis B surface (HBs antigen) or hepatitis C virus (HCV antibody)
- •Participants who have taken lenvatinib before
- •Participants who in the view of the principal investigator or sub-investigator are not able to comply with this protocol because of psychiatric or physical diseases including alcoholism or drug addiction
- •Pregnant or nursing participants
- •Participants who are participating in another clinical trial
研究组 & 干预措施
24 mg lenvatinib
Participants will receive once daily oral dosing of lenvatinib 24 milligrams (mg)
干预措施: lenvatinib (Drug)
结局指标
主要结局
Area under the concentration-time curve over the dosing interval on multiple dosing (AUC[0-τ])
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. AUC(0-τ) is defined as the area under the concentration-time profile from time zero to the end of the dosing interval at steady state. AUC represents the total drug exposure over a defined period of time.
Time at which the highest drug concentration occurs at steady-state (tss,max)
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. tss,max is the time at which the maximum concentration of lenvatinib is observed in the plasma at steady state, which occurs when the rates of drug administration and drug elimination are equal.
Average steady-state concentration (Css,av)
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,av is the average concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when the rates of drug administration and drug elimination are equal.
Minimum observed concentration at steady-state (Css,min)
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,min is the lowest concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when the rates of drug administration and drug elimination are equal.
Maximum observed concentration at steady-state (Css,max)
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,max is the highest concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when rates of drug administration and drug elimination are equal.
Area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC[0-t])
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)
Blood samples will be collected to determine the plasma lenvatinib concentration at various time points. AUC(0-t) is defined as the AUC from time "0" to the time of the last measurable concentration. AUC represents the total drug exposure over a defined period of time.
Time at which the highest drug concentration occurs (tmax)
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Tmax is the time at which the maximum concentration of lenvatinib is observed in plasma after a single dose of lenvatinib.
Maximum observed concentration (Cmax)
时间窗: Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)
Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Cmax is the highest concentration of lenvatinib observed in plasma after a single dose of lenvatinib.
次要结局
- Mean pulse(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean blood urea nitrogen (BUN) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean creatinine values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean albumin values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean cholesterol values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean lactate dehydrogenase values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean total protein values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean C-reactive protein (CRP) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean gamma-glutamyl transpeptidase (γ-GTP) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean total bilirubin values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean alanine transaminase (ALT) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean aspartate transaminase (AST) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean alkaline phosphatase (ALP) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean body temperature(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean body weight(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean heart rate(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean QT values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean QT corrected (QTc) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean QTc corrected using Fridericia's method (QTcF) values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Number of participants with abnormal, clinically significant physical examination findings(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean calcium values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean chloride values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean potassium values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean sodium values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean lymphocyte count(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean neutrophil count(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean white blood cell (WBC) count(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean platelet count(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean hemoglobin values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean red blood cell (RBC) count(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Number of participants with any serious adverse event and any non-serious adverse event(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean protein in urine values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean glucose in urine values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean occult blood in urine values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))
- Mean systolic blood pressure and diastolic blood pressure values(until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28))