A Study in Healthy Men to Test Whether Zongertinib Influences the Amount of 4 Other Medicines (Dabigatran, Rosuvastatin, Metformin, and Furosemide) in the Blood

Boehringer Ingelheim32 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

ZongertinibDRUG

A 120 mg dose on Day 1 of period 2 (Part 1) OR daily (Part 2) with 240 mL of water after an overnight fast of at least 10 hours.

Dabigatran-etexilateDRUG

A 150 mg dose on Day 1 of each period with 240 mL of water after an overnight fast of at least 10 hours.

RosuvastatinDRUG

A 10 mg dose on Day 1 of each period with 240 mL of water after an overnight fast of at least 10 hours.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria : * 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 Exclusion Criteria : * 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.

Locations (1)

Humanpharmakologisches Zentrum Biberach

Biberach, Germany

Outcomes

Primary Outcomes

Part 1: Area Under the Concentration-time Curve of Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

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.

Time frame: 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 1: Maximum Measured Concentration of Dabigatran in Plasma (Cmax)

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-∞)

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.

Data from ClinicalTrials.gov

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A 10 mg dose on Day 1 of each period with 240 mL of water after an overnight fast of at least 10 hours.

FurosemideDRUG

A 1 mg dose on Day 1 of each period with 240 mL of water after an overnight fast of at least 10 hours.

Time frame: 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: Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax)

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-∞)

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)

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-∞)

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)

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.

Secondary Outcomes

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)

Area under the concentration-time curve of dabigatran in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) 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 to the Last Quantifiable Data Point (AUC0-tz)

Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) 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 to the Last Quantifiable Data Point (AUC0-tz)

Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) 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 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

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) 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.