The Effect of Zongertinib on the Pharmacokinetics of Dabigatran (Part 1) and Rosuvastatin, Metformin and Furosemide Administered as a Cocktail (Part 2) in Healthy Male Subjects (a 2-part, Open-label, 2-period, Fixed-sequence Cross-over Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Part 1: Area Under the Concentration-time Curve of Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
研究概览
简要总结
For Part 1 of the trial, the main objective is to assess the effect of a single dose of zongertinib on the pharmacokinetics of a single dose of dabigatran-etexilate. For Part 2 of the trial, the main objective is to assess the effect of zongertinib at steady-state on the pharmacokinetics of a single dose of rosuvastatin, metformin and furosemide (administered as a cocktail).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 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 in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
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
Part 1: dabigatran-etexilate (R), then zongertinib and dabigatran-etexilate (T)
Participants were administered a 150 milligram (mg) dabigatran-etexilate hard capsule orally with 240 milliliters (mL) of water after an overnight fast of at least 10 hours on Day 1 of period 1 (Reference treatment, R). After a wash-out period, participants were administered two 60 mg film-coated tablets of zongertinib (total dose: 120 mg) orally, and a 150 mg dabigatran-etexilate hard capsule orally on Day 1 of period 2 (Test treatment, T). Both medications were administered with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: Zongertinib (Drug)
Part 1: dabigatran-etexilate (R), then zongertinib and dabigatran-etexilate (T)
Participants were administered a 150 milligram (mg) dabigatran-etexilate hard capsule orally with 240 milliliters (mL) of water after an overnight fast of at least 10 hours on Day 1 of period 1 (Reference treatment, R). After a wash-out period, participants were administered two 60 mg film-coated tablets of zongertinib (total dose: 120 mg) orally, and a 150 mg dabigatran-etexilate hard capsule orally on Day 1 of period 2 (Test treatment, T). Both medications were administered with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: Dabigatran-etexilate (Drug)
Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)
Participants were administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution with 240 mL of water after an overnight fast of at least 10 hours on Day 1 of period 1 (Reference treatment, R). In period 2, from Day -9 to Day 3, participants were administered two 60 mg film-coated tablets of zongertinib (total dose: 120 mg) orally every day. On Day 1, participants were also administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution (Test treatment, T). Every medication was administered with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: Zongertinib (Drug)
Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)
Participants were administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution with 240 mL of water after an overnight fast of at least 10 hours on Day 1 of period 1 (Reference treatment, R). In period 2, from Day -9 to Day 3, participants were administered two 60 mg film-coated tablets of zongertinib (total dose: 120 mg) orally every day. On Day 1, participants were also administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution (Test treatment, T). Every medication was administered with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: Rosuvastatin (Drug)
Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)
Participants were administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution with 240 mL of water after an overnight fast of at least 10 hours on Day 1 of period 1 (Reference treatment, R). In period 2, from Day -9 to Day 3, participants were administered two 60 mg film-coated tablets of zongertinib (total dose: 120 mg) orally every day. On Day 1, participants were also administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution (Test treatment, T). Every medication was administered with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: Metformin hydrochloride (Drug)
Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)
Participants were administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution with 240 mL of water after an overnight fast of at least 10 hours on Day 1 of period 1 (Reference treatment, R). In period 2, from Day -9 to Day 3, participants were administered two 60 mg film-coated tablets of zongertinib (total dose: 120 mg) orally every day. On Day 1, participants were also administered a cocktail consisting of a 10 mg rosuvastatin film-coated tablet, a 10 mg metformin oral solution, and a 1 mg furosemide oral solution (Test treatment, T). Every medication was administered with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: Furosemide (Drug)
结局指标
主要结局
Part 1: Area Under the Concentration-time Curve of Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
时间窗: Within 3 hours (h) before dabigatran-etexilate administration (R only), within 3 h prior to zongertinib administration (T only), and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48 h after dabigatran-etexilate administration (R and T).
Area under the concentration-time curve of dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
Part 1: Maximum Measured Concentration of Dabigatran in Plasma (Cmax)
时间窗: Within 3 hours (h) before dabigatran-etexilate administration (R only), within 3 h prior to zongertinib administration (T only), and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48 h after dabigatran-etexilate administration (R and T).
Maximum measured concentration of dabigatran in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an ANOVA model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
Part 2: Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
时间窗: Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).
Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an ANOVA model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
Part 2: Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax)
时间窗: Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).
Maximum measured concentration of rosuvastatin in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an ANOVA model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
Part 2: Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
时间窗: Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).
Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an ANOVA model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
Part 2: Maximum Measured Concentration of Metforminin in Plasma (Cmax)
时间窗: Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).
Maximum measured concentration of metforminin in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an ANOVA model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
Part 2: Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
时间窗: Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).
Area under the concentration-time curve of furosemide in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an ANOVA model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
Part 2: Maximum Measured Concentration of Furosemide in Plasma (Cmax)
时间窗: Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).
Maximum measured concentration of furosemide in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an ANOVA model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: participant (considered as random) and treatment (considered as fixed). These quantities were then back-transformed to the original scale.
次要结局
- Part 1: Area Under the Concentration-time Curve of Dabigatran in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Within 3 hours (h) before dabigatran-etexilate administration (R only), within 3 h prior to zongertinib administration (T only), and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48 h after dabigatran-etexilate administration (R and T).)
- Part 2: Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).)
- Part 2: Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).)
- Part 2: Area Under the Concentration-time Curve of Furosemide in in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Within 3 h prior to drug cocktail administration (R), within 15 minutes prior to drug cocktail and zongertinib administration (T), and 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after drug cocktail administration (R and T).)