A Study in Healthy Men to Test How Zongertinib (BI 1810631) is Taken up and Processed by the Body

A Phase I, Open-label Trial in Two Parallel Parts to Investigate Mass Balance, Metabolism, and Basic Pharmacokinetics of BI 1810631 (C-14) Administered as Oral Solution (Part A) and to Investigate Absolute Bioavailability of BI 1810631 Administered as Film-coated Tablet Together With an Intravenous Microtracer Dose of BI 1810631 (C-14) (Part B) in Healthy Male Volunteers

Part A - the primary objective is to assess the mass balance and total recovery of [14C]-radioactivity in urine and faeces after oral single dose administration of BI 1810631 (C-14) (test treatment T1) in healthy male subjects.

Part A - the secondary objective is to assess concentrations of BI 1810631 and [14C]-radioactivity in plasma.

Part B - the primary objective is to investigate the absolute bioavailability of BI 1810631 administered as film-coated tablet (test treatment T2, not radio-labelled) compared with BI 1810631 (C-14) (reference treatment R) administered as intravenous microtracer.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: zongertinib (C-14); Drug: zongertinib (C-14); Drug: zongertinib

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • ICON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 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
2. Age of 18 to 55 years (inclusive)
3. Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive)
4. 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:

1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 90 to 145 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 45 to 90 mmHg, or pulse rate outside the range of 40 to 100 beats per minute (bpm)
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
8. History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A - zongertinib (C-14) (T1); Healthy male subjects were administered a single oral dose of radioactively-labelled zongertinib (C-14) as a solution (test treatment 1 [T1]) with 240 milliliter (mL) of water, after an overnight fast of at least 10 hours (h). The solution contained a mixture of pure [14C]-labelled zongertinib ("hot") drug substance, and zongertinib, i.e. unlabeled ("cold") drug substance, and it contained a radioactive dose of approximately 3.7 Megabecquerel (MBq).	Drug: zongertinib (C-14); Oral solution; Other Names: BI 1810631 (C-14), Hernexeos®; Drug: zongertinib (C-14); Solution for infusion; Other Names: BI 1810631 (C-14), Hernexeos®
Experimental: Part B - zongertinib (T2), then zongertinib (C-14) (R); Healthy male subjects were administered one zongertinib film-coated tablet (test treatment 2 [T2]) orally with 240 mL of water after an overnight fast of at least 10 h. Two hours later, subjects were administered a single solution of radioactively-labelled zongertinib (C-14) (reference treatment [R]) via intravenous infusion. The solution contained a mixture of pure [14C]-labelled zongertinib ("hot") drug substance and zongertinib, i.e. unlabelled ("cold") drug substance, and contained a radioactive dose of approximately 0.03 MBq.	Drug: zongertinib (C-14); Oral solution; Other Names: BI 1810631 (C-14), Hernexeos®; Drug: zongertinib (C-14); Solution for infusion; Other Names: BI 1810631 (C-14), Hernexeos®; Drug: zongertinib; Film-coated tablet; Other Names: BI 1810631, Hernexeos®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B - Dose-normalised Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞,Norm)	The dose-normalised area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞,norm) after oral administration of zongertinib, and after intravenous administration of [14C]zongertinib, 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 PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included the effect 'subjects' as a random effect and 'treatment' as a fixed effect. These quantities were then back-transformed to the original scale.	Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, [zongertinib], 2, 2.08, 2.16, 2.25, 2.5, 2.75, 3, 3.5 [[14C]zongertinib], 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, and 168 h [zongertinib and [14C]zongertinib] after first drug administration.
Part A - Fraction Excreted in Urine and Faeces as Percentage of the Administered Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe0-tz)	Mass balance and total recovery of [14C]-radioactivity: fraction excreted in urine and faeces given as percentage of the administered oral dose of zongertinib (assessed by [14C]zongertinib-equivalent[EQ]) over the time interval from 0 to the last quantifiable time point (feurine, 0-tz; fefaeces, 0-tz) is reported. Timeframe (continued): after 336 h, if warranted, 24 h collections were to be performed every 7 days on days 21, 28, 35, and 42. Sampling was stopped when the release criteria for radioactivity recovery were met (earliest stopping on Day 15).	Within 18 h (urine) or 48 h (faeces) before drug intake; at 0-4, 4-8, 8-12, 12-24 (urine); and at 24 h sampling intervals until 336 h after drug intake (both). Both: after 336 h, every 7 days, up to day 42. Continues in description.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A - Maximum Measured Concentration of Zongertinib in Plasma (Cmax)	Maximum measured concentration of zongertinib in plasma (Cmax) is reported.	Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.
Part A - Maximum Measured Concentration of [14C]-Radioactivity (Assessed by [14C]Zongertinib-EQ) in Plasma (Cmax)	Maximum measured concentration of [14C]-radioactivity (assessed by [14C]zongertinib-EQ) in plasma (Cmax) is reported.	Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.
Part A - Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz)	Area under the concentration-time curve of zongertinib in plasma over the time interval from 0 to the last quantifiable time point (AUC0-tz) is reported.	Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.
Part A - Area Under the Concentration-time Curve of [14C]-Radioactivity (Assessed by [14C]Zongertinib-EQ) in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz)	Area under the concentration-time curve of [14C]-radioactivity (assessed by [14C]zongertinib-EQ) in plasma over the time interval from 0 to the last quantifiable time point (AUC0-tz) is reported.	Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.
Part B - Dose-normalised Maximum Measured Concentration in Plasma (Cmax,Norm)	The dose-normalised maximum measured concentration in plasma (Cmax,norm) after oral administration of zongertinib, and after intravenous administration of [14C]zongertinib, 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 the effect 'subjects' as a random effect and 'treatment' as a fixed effect. These quantities were then back-transformed to the original scale.	Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, [zongertinib], 2, 2.08, 2.16, 2.25, 2.5, 2.75, 3, 3.5 [[14C]zongertinib], 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, and 168 h [zongertinib and [14C]zongertinib] after first drug administration.
Part B - Dose-normalised Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz,Norm)	The dose-normalised area under the concentration-time curve in plasma over the time interval from 0 to the last quantifiable time point (AUC0-tz,norm) after oral administration of zongertinib, and after intravenous administration of [14C]zongertinib, 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 the effect 'subjects' as a random effect and 'treatment' as a fixed effect. These quantities were then back-transformed to the original scale.	Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, [zongertinib], 2, 2.08, 2.16, 2.25, 2.5, 2.75, 3, 3.5 [[14C]zongertinib], 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, and 168 h [zongertinib and [14C]zongertinib] after first drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): October 19, 2023
• Study Completion (Actual): October 19, 2023

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: May 25, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Carbon-14
• Other Study ID Numbers: 1479-0006; 2022-503047-17-00 (Registry Identifier: CTIS); U1111-1291-2883 (Registry Identifier: WHO registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No