Phase 1, Open-label, Single Sequence, Two-Period Crossover Trial to Evaluate the Effect of Tepotinib on CYP3A by Investigating the PK of the CYP3A Substrate Midazolam in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- 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 Midazolam
研究概览
简要总结
The study investigated the effect of tepotinib on the pharmacokinetics (PK) of the Cytochrome P450 (CYP) 3A substrate midazolam determined from concentrations of midazolam and its main metabolite 1-hydroxymidazolam in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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)
- •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
Midazolam (Reference Treatment)
Participants received single oral dose of 7.5 milligrams (mg) midazolam tablet on Day 1 of treatment period 1. The washout period between midazolam administrations in Period 1 and Period 2 was 12 days.
干预措施: Midazolam (Drug)
Tepotinib + Midazolam (Test Treatment)
All participants who received 7.5 mg midazolam tablet in treatment period 1 received single oral dose of 500 mg tepotinib film-coated tablet from Day 1 to 11 along with 7.5 mg midazolam tablet on Day 11 in treatment period 2.
干预措施: Midazolam (Drug)
Tepotinib + Midazolam (Test Treatment)
All participants who received 7.5 mg midazolam tablet in treatment period 1 received single oral dose of 500 mg tepotinib film-coated tablet from Day 1 to 11 along with 7.5 mg midazolam tablet on Day 11 in treatment period 2.
干预措施: Tepotinib (Drug)
结局指标
主要结局
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 Midazolam
时间窗: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2
AUC0-t a Pharmacokinetic (PK) parameter 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 Midazolam
时间窗: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2
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).
Maximum Observed Plasma Concentration (Cmax) of Midazolam
时间窗: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2
Cmax was obtained directly from concentration versus time curve.
次要结局
- Time to Reach Maximum Plasma Concentration (Tmax) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam)(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death(Baseline (Day 1 of treatment period 1) up to the End of Trial visit (Day 20))
- 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 Midazolam Metabolite (1-Hydroxymidazolam)(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2)
- Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam Metabolite (1-Hydroxymidazolam)(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2)
- Maximum Observed Plasma Concentration (Cmax) of Midazolam Metabolite (1-Hydroxymidazolam)(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2)
- Metabolic Ratio of Midazolam and Midazolam Metabolite (1-hydroxymidazolam)(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2)
- Elimination Half Life (t1/2) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam)(Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2)
- Number of Participants With Clinically Significant Changes in Laboratory Values(From Screening up to the End of Trial visit (Day 20))
- Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)(Day 1 (Treatment Period 1) up to the End of Trial visit (Day 20))
- Number of Participants With Clinically Significant Changes in Vital Signs(Day 1 (Treatment Period 1) up to the End of Trial visit (Day 20))