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

NCT05879991 | Completed Phase 1 Results

• 3 other identifiers: 1479-00062022-503047-17-00U1111-1291-2883
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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.

• 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.

Secondary Outcomes (6)

• Part A - Maximum Measured Concentration of Zongertinib in Plasma (Cmax)

  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)

  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)

  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)

  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)

  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.

Study Arms (2)

Part A - zongertinib (C-14) (T1)

EXPERIMENTAL

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)

Part B - zongertinib (T2), then zongertinib (C-14) (R)

EXPERIMENTAL

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; Drug: zongertinib (C-14)

Interventions

zongertinib (C-14) DRUG

Oral solution

Also known as: BI 1810631 (C-14), Hernexeos®

Part A - zongertinib (C-14) (T1)

zongertinib DRUG

Film-coated tablet

Also known as: BI 1810631, Hernexeos®

Part B - zongertinib (T2), then zongertinib (C-14) (R)

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 18.0 to 30.0 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 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)
• 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
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

ICON

Groningen, 9728 NZ, Netherlands

Location

Related Publications (1)

• Grempler R, Joseph D, Gan G, Auclair AM, Tiessen RG, Maw HH, Laux R, Wind S, Roessner PM, Sadrolhefazi B, Muller F, Minich D. Absorption, Metabolism, Distribution and Excretion (ADME) and Absolute Bioavailability Assessment of Zongertinib in Healthy Male Volunteers. Clin Drug Investig. 2025 Dec 5. doi: 10.1007/s40261-025-01509-9. Online ahead of print.

  PMID: 41348300 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Carbon-14

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: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: May 30, 2023
• Study Start: August 10, 2023
• Primary Completion: October 19, 2023
• Study Completion: October 19, 2023
• Last Updated: October 6, 2025
• Results First Posted: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)