NCT03492437已完成1 期
Phase I, Open-label, Single Sequence, Two-Period Study to Evaluate the Effect of Tepotinib on P-gp by Investigating the PK of the P-gp Probe Substrate Dabigatran Etexilate in Healthy Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran
研究概览
简要总结
This study investigated the effect of Tepotinib on the pharmacokinetics (PK) of the p-glycoprotein (P-gp) probe substrate Dabigatran etexilate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 44 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants of non-child bearing potential
- •Body weight between 50 to 100 kilogram (kg)
- •Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m^2)
- •A male participant must agree to use and to have his female partner of childbearing potential to use highly effective method of contraception
- •Participant must have given written informed consent before any study-related activities
- •All values for hematology, coagulation, and biochemistry tests of blood and urinalysis are within the normal range. Minor (solitary) non-clinically relevant deviation(s) are allowed as judged by the Investigator
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participation in a clinical study within 60 days prior to first drug administration
- •Whole blood donation or loss of > 450 milliliter (mL) within 60 days prior to first drug administration
- •Any surgical or medical condition, or any other significant disease that could interfere with the study objectives, conduct, or evaluation
- •Supine systolic blood pressure (SBP) greater than (>) 140 millimeter of mercury (mmHg) or less than (<) 90 mmHg, diastolic blood pressure (DBP) > 90 or < 50 mmHg, and pulse rate > 90 or <50 beats per minute (bpm) at Screening and at admission on Day-
- •12-Lead electrocardiograms (ECG) showing a corrected QT interval per Fridericia's formula (QTcF) > 450 milliseconds (ms), PR > 215 ms, or QRS > 120 ms (at Screening)
- •Creatinine clearance estimated glomerular filtration rate (eGFR) < 90 milliliter per minute (mL/min) (at Screening)
- •Participants with gall bladder removal or other relevant surgery of gastrointestinal tract
- •History of any malignancy
- •History of epilepsy
- •Ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or excipients
- •Participants who in the Investigator's judgment were perceived as having an increased risk of bleeding
- •Positive screen for alcohol or drugs of abuse (at Screening and Day -1)
- •Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), and human immunodeficiency virus 1 and 2 antibodies (HIV1/HIV2 antibodies) (at Screening)
- •Excessive consumption of xanthine-containing food or beverages before study drug administration until collection of last pharmacokinetic (PK) sample in each period (at Screening and Day -1)
- •Receipt of any prescription or nonprescription medication within 14 days or 5 half-lives, before study drug administration
- •Smoker or former smoker who stopped smoking less than 6 months before the time of the Screening Visit
- •Intake of grapefruit, Seville orange, cranberry or juices of these 3 fruits, or St. John's Wort, from 14 days prior to Day -1
- •Inability to communicate or cooperate with the Investigator
- •Other factors, which in the opinion of the Investigator may interfere with study conduct (at Screening and Day -1 of first Period only)
- •Legal incapacity or limited legal capacity
- •Participants kept in detention
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Dabigatran Etexilate
Experimental
干预措施: Dabigatran Etexilate (Drug)
Tepotinib + Dabigatran
Experimental
干预措施: Dabigatran Etexilate (Drug)
Tepotinib + Dabigatran
Experimental
干预措施: Tepotinib (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran
时间窗: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Cmax was obtained directly from the concentration versus time curve.
Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total Dabigatran
时间窗: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
AUC0-t was calculated according to the mixed log linear trapezoidal rule.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Dabigatran
时间窗: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
AUC0-inf was calculated as AUC0-t plus (+) AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/Lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log-linear regression line for Lambda z determination at which the measured plasma concentration is at or above Lower limit of quantification (LLOQ).
次要结局
- Time to Reach Maximum Plasma Concentration (Tmax) of Total Dabigatran(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8)
- Apparent Volume of Distribution During Terminal Phase (Vz/f) of Total Dabigatran(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8)
- Percentage of Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Total Dabigatran(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8)
- Elimination Half Life (t1/2) of Total Dabigatran(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs(Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2)
- Number of Participants With Clinically Significant Changes in Laboratory Values(Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2)
- Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Findings(Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2)
- Apparent Clearance (CL/f) of Total Dabigatran(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8)
- Number of Participants With Clinically Significant Changes in Vital Signs(Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2)
研究者
研究点 (1)
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