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

NCT06504862 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 1479-00152024-510628-38-00U1111-1302-1171
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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 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.

  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.

  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 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.

  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 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.

  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 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.

  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 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.

  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).

Secondary Outcomes (4)

• 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).

Study Arms (2)

Part 1: dabigatran-etexilate (R), then zongertinib and dabigatran-etexilate (T)

EXPERIMENTAL

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.

Drug: Zongertinib; Drug: Dabigatran-etexilate

Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)

EXPERIMENTAL

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.

Drug: Zongertinib; Drug: Rosuvastatin; Drug: Metformin hydrochloride; Drug: Furosemide

Interventions

Zongertinib DRUG

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.

Also known as: Hernexeos®

Part 1: dabigatran-etexilate (R), then zongertinib and dabigatran-etexilate (T); Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)

Dabigatran-etexilate DRUG

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

Also known as: Pradaxa®

Part 1: dabigatran-etexilate (R), then zongertinib and dabigatran-etexilate (T)

Rosuvastatin DRUG

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

Also known as: Crestor®

Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)

Metformin hydrochloride DRUG

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

Also known as: MetfoLiquid GeriaSan®

Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)

Furosemide DRUG

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

Also known as: Lasix®

Part 2: drug cocktail (R), then zongertinib and drug cocktail (T)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Location

Related Links

• Related Info

MeSH Terms

Interventions

Dabigatran; Rosuvastatin Calcium; Metformin; Furosemide

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Biguanides; Guanidines; Amidines; Sulfanilamides; Aniline Compounds; Amines

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: OTHER

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: fixed-sequence crossover

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 17, 2024
• Study Start: August 20, 2024
• Primary Completion: October 3, 2024
• Study Completion: December 18, 2024
• Last Updated: January 9, 2026
• Results First Posted: January 9, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)