The Effect of Multiple Doses of Zongertinib on the Single-dose Pharmacokinetics of Midazolam, Omeprazole and Repaglinide in Healthy Male Subjects (an Open-label, 2-period, Fixed-sequence Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞)
研究概览
简要总结
The main objective of this trial is to assess the effect of multiple oral doses of zongertinib on the pharmacokinetics of midazolam, omeprazole and repaglinide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
- •Age of 18 to 55 years (inclusive)
- •Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent
排除标准
- •Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
- •Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre(s) of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (bpm)
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator Further exclusion criteria apply.
研究组 & 干预措施
Repaglinide+Midazolam+Omeprazole (Reference)/ Zongertinib+Repaglinide+Midazolam+Omeprazole (Test)
Reference (Repaglinide + Midazolam + Omeprazole)
In the reference treatment period (Period 1), participants received 0.5 mg repaglinide tablet (Day 1, after ≥10 h fast; Reference Treatment 1). On Day 2, they received 1 mg midazolam (0.5 mL oral solution) with 20 mg omeprazole tablet under the same fasting conditions (Reference Treatment 2).
Test (Zongertinib + Repaglinide + Midazolam + Omeprazole)
In the test treatment period (Period 2), participants received multiple once-daily doses of 120 mg zongertinib from Day 1 to Day 15. A single 0.5 mg repaglinide tablet was co-administered on Day 1 (Test Treatment 1) and Day 14 (Test Treatment 3), and a single dose of the probe drug cocktail containing 1 mg midazolam (0.5 mL oral solution) and 20 mg omeprazole tablet was co-administered on Day 2 (Test Treatment 2) and Day 15 (Test Treatment 4).
干预措施: zongertinib (Drug)
Repaglinide+Midazolam+Omeprazole (Reference)/ Zongertinib+Repaglinide+Midazolam+Omeprazole (Test)
Reference (Repaglinide + Midazolam + Omeprazole)
In the reference treatment period (Period 1), participants received 0.5 mg repaglinide tablet (Day 1, after ≥10 h fast; Reference Treatment 1). On Day 2, they received 1 mg midazolam (0.5 mL oral solution) with 20 mg omeprazole tablet under the same fasting conditions (Reference Treatment 2).
Test (Zongertinib + Repaglinide + Midazolam + Omeprazole)
In the test treatment period (Period 2), participants received multiple once-daily doses of 120 mg zongertinib from Day 1 to Day 15. A single 0.5 mg repaglinide tablet was co-administered on Day 1 (Test Treatment 1) and Day 14 (Test Treatment 3), and a single dose of the probe drug cocktail containing 1 mg midazolam (0.5 mL oral solution) and 20 mg omeprazole tablet was co-administered on Day 2 (Test Treatment 2) and Day 15 (Test Treatment 4).
干预措施: midazolam (Drug)
Repaglinide+Midazolam+Omeprazole (Reference)/ Zongertinib+Repaglinide+Midazolam+Omeprazole (Test)
Reference (Repaglinide + Midazolam + Omeprazole)
In the reference treatment period (Period 1), participants received 0.5 mg repaglinide tablet (Day 1, after ≥10 h fast; Reference Treatment 1). On Day 2, they received 1 mg midazolam (0.5 mL oral solution) with 20 mg omeprazole tablet under the same fasting conditions (Reference Treatment 2).
Test (Zongertinib + Repaglinide + Midazolam + Omeprazole)
In the test treatment period (Period 2), participants received multiple once-daily doses of 120 mg zongertinib from Day 1 to Day 15. A single 0.5 mg repaglinide tablet was co-administered on Day 1 (Test Treatment 1) and Day 14 (Test Treatment 3), and a single dose of the probe drug cocktail containing 1 mg midazolam (0.5 mL oral solution) and 20 mg omeprazole tablet was co-administered on Day 2 (Test Treatment 2) and Day 15 (Test Treatment 4).
干预措施: omeprazole (Drug)
Repaglinide+Midazolam+Omeprazole (Reference)/ Zongertinib+Repaglinide+Midazolam+Omeprazole (Test)
Reference (Repaglinide + Midazolam + Omeprazole)
In the reference treatment period (Period 1), participants received 0.5 mg repaglinide tablet (Day 1, after ≥10 h fast; Reference Treatment 1). On Day 2, they received 1 mg midazolam (0.5 mL oral solution) with 20 mg omeprazole tablet under the same fasting conditions (Reference Treatment 2).
Test (Zongertinib + Repaglinide + Midazolam + Omeprazole)
In the test treatment period (Period 2), participants received multiple once-daily doses of 120 mg zongertinib from Day 1 to Day 15. A single 0.5 mg repaglinide tablet was co-administered on Day 1 (Test Treatment 1) and Day 14 (Test Treatment 3), and a single dose of the probe drug cocktail containing 1 mg midazolam (0.5 mL oral solution) and 20 mg omeprazole tablet was co-administered on Day 2 (Test Treatment 2) and Day 15 (Test Treatment 4).
干预措施: repaglinide (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞)
时间窗: Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule
The area under the concentration-time curve of repaglinide in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose.
Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞)
时间窗: Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule
The area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose.
Maximum Measured Concentration of Repaglinide in Plasma (Cmax)
时间窗: Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule
The maximum measured concentration of repaglinide in plasma is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose.
Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞)
时间窗: Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule
The area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose.
Maximum Measured Concentration of Midazolam in Plasma (Cmax)
时间窗: Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule
The maximum measured concentration of midazolam in plasma is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose.
Maximum Measured Concentration of Omeprazole in Plasma (Cmax)
时间窗: Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule
The maximum measured concentration of omeprazole in plasma is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose.
次要结局
- Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule)
- Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule)
- Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule)