Phase 1, Open-label, 3-Parts Study With Crossover Design in Each Part to Investigate the Bioequivalence of the Tablet Formulation of TF3 Compared to TF2 (Part A), and to Investigate the Influence of Food on the PK of Each TF2 (Part B) and TF3 (Part C) of Tepotinib in Healthy 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 A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib
研究概览
简要总结
The main purpose of the study was to demonstrate bioequivalence between the new tablet formulation (TF3, test treatment) and the tablet formulation used in clinical studies (TF2, reference treatment) and to investigate effect of food on pharmacokinetics (PK) of tepotinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •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)
- •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 greater than 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
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Part A: First Tepotinib TF2 then TF3
Participants received a single oral dose of 500 milligrams (mg) Tepotinib tablet formulation 2 (TF2, reference treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib tablet formulation 3 (TF3, test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF2 (Drug)
Part A: First Tepotinib TF2 then TF3
Participants received a single oral dose of 500 milligrams (mg) Tepotinib tablet formulation 2 (TF2, reference treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib tablet formulation 3 (TF3, test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF3 (Drug)
Part A: First Tepotinib TF3 then TF2
Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF2 (Drug)
Part A: First Tepotinib TF3 then TF2
Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF3 (Drug)
Part B: First Tepotinib TF2 Fasted then TF2 Fed
Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF2 (Drug)
Part B: First Tepotinib TF2 Fed then TF2 Fasted
Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF2 (Drug)
Part C: First Tepotinib TF3 Fasted then TF3 Fed
Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF3 (Drug)
Part C: First Tepotinib TF3 Fed then TF3 Fasted
Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.
干预措施: Tepotinib TF3 (Drug)
结局指标
主要结局
Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib
时间窗: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Tepotinib
时间窗: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Part A, B and C: Maximum Observed Plasma Concentration (Cmax) of Tepotinib
时间窗: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period
Cmax was obtained directly from the concentration versus time curve.
次要结局
- Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings(Time from date of informed consent signature up to end of study (assessed up to 7 weeks))
- Number of Participants With Clinically Significant Abnormalities in Vital Signs(Time from date of informed consent signature up to end of study (assessed up to 7 weeks))
- Part A, B and C: Apparent Volume of Distribution of Tepotinib During the Terminal Phase Following Extravascular Administration (Vz/f)(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period)
- Number of Participants With Clinically Significant Abnormalities in Laboratory Values(Time from date of informed consent signature up to end of study (assessed up to 7 weeks))
- Part A, B and C: Terminal Half-Life (t1/2) of Tepotinib(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs(Time from date of informed consent signature up to end of study (assessed up to 7 weeks))
- Part A, B and C: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period)
- Part A, B and C: Apparent Total Body Clearance of Tepotinib From Plasma Following Oral Administration (CL/f)(Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period)