Phase I, Open-label, Three-Period Crossover Study to Investigate the Effect of a Proton Pump Inhibitor (Omeprazole) on the PK of Tepotinib 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
- Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C
研究概览
简要总结
This study was investigated in healthy participants (i) the effect of omeprazole (proton pump inhibitor) co-administration on the single dose pharmacokinetics (PK) of tepotinib under fed conditions, and (ii) the effect of food on the single dose PK of tepotinib after co-administration of omeprazole and tepotinib. Furthermore, the study assessed the safety and tolerability of tepotinib alone and upon co-administration of omeprazole.
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 mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m^2)
- •Body weight between 50 to 100 kilogram (kg)
- •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
Sequence 1: Treatment A-B-C
Participants received single oral dose of 500 milligrams (mg) of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Tepotinib (Drug)
Sequence 1: Treatment A-B-C
Participants received single oral dose of 500 milligrams (mg) of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Omeprazole (Drug)
Sequence 2: Treatment A-C-B
Participants received single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Tepotinib (Drug)
Sequence 2: Treatment A-C-B
Participants received single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Omeprazole (Drug)
Sequence 3: Treatment B-A-C
Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Tepotinib (Drug)
Sequence 3: Treatment B-A-C
Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Omeprazole (Drug)
Sequence 4: Treatment B-C-A
Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Tepotinib (Drug)
Sequence 4: Treatment B-C-A
Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Omeprazole (Drug)
Sequence 5: Treatment C-A-B
Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Tepotinib (Drug)
Sequence 5: Treatment C-A-B
Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Omeprazole (Drug)
Sequence 6: Treatment C-B-A
Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Tepotinib (Drug)
Sequence 6: Treatment C-B-A
Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.
干预措施: Omeprazole (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C
时间窗: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
Cmax was obtained directly from the concentration versus time curve.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C
时间窗: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
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.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C
时间窗: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
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.
次要结局
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B)
- Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B)
- Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Tepotinib in Treatments A, B and C(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C))
- Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C))
- Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs(Baseline up to Day 4 for Treatment A and up to Day 8 for Treatment B and C)
- Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B)
- Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C))
- Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C(Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C))