An Open-label, Single-dose, Randomized, 2-period, 2-sequence Cross-over, Single-center Phase I Trial in Healthy Subjects to Assess the Bioequivalence of Tepotinib TF3 Administered as 5 Tablets of 100 mg Versus 2 Tablets of 250 mg Dose Strength
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib
研究概览
简要总结
This study investigated the bioequivalence of the 100 milligrams (mg) and 250 mg dose strengths of tepotinib tablet formulation 3 (TF3) when administered at the same dose under fasted condition.
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
Test Treatment then Reference Treatment
Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 1 followed by a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.
干预措施: Tepotinib 100 mg (Drug)
Test Treatment then Reference Treatment
Participants received a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 1 followed by a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.
干预措施: Tepotinib 250 mg (Drug)
Reference Treatment then Test Treatment
Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 1 followed by a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.
干预措施: Tepotinib 100 mg (Drug)
Reference Treatment then Test Treatment
Participants received a single oral dose of reference treatment of tepotinib TF3 (2 * 250 mg) in treatment period 1 followed by a single oral dose of test treatment of tepotinib TF3 (5 * 100 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.
干预措施: Tepotinib 250 mg (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib
时间窗: Pre-dose, 0.25, 0.50, 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
AUC0-inf was calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Tepotinib
时间窗: Pre-dose, 0.25, 0.50, 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
Area under the plasma concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log linear trapezoidal rule (linear up/log down).
Maximum Observed Plasma Concentration (Cmax) of Tepotinib
时间窗: Pre-dose, 0.25, 0.50, 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
Cmax was obtained directly from the concentration versus time curve.
次要结局
- Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs(Baseline up to Day 59)
- Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib(Pre-dose, 0.25, 0.50, 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)
- Terminal Half-Life (t1/2) of Tepotinib(Pre-dose, 0.25, 0.50, 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)
- Apparent Volume of Distribution During Terminal Phase (Vz/f) for Tepotinib(Pre-dose, 0.25, 0.50, 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)
- Apparent Total Body Clearance (CL/f) of Tepotinib(Pre-dose, 0.25, 0.50, 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)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation(Baseline up to Day 59)