A Study in Healthy Men to Test Whether Carbamazepine Influences the Amount of Zongertinib in the Blood

Phase 1

Completed

Brief Summary: The main objective of this trial is to investigate the effect of multiple oral doses of the strong CYP3A inducer carbamazepine on the pharmacokinetics of a single dose of BI 1810631 in plasma.

Recruitment & Eligibility

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 ICH-GCP and local legislation prior to admission to the trial

Exclusion Criteria

Any finding in the medical examination (including BP, PR or ECG, the neurological examination, or the skin inspection) deviating from normal and assessed as clinically relevant by the investigator
Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 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
History of relevant orthostatic hypotension, fainting spells, or blackouts
Further exclusion criteria apply

Arm && Interventions

Group	Intervention	Description
Zongertinib Alone (Reference)/ Zongertinib+Carbamazepine (Test)	Zongertinib	Participants took a single 60 mg oral dose of Zongertinib after fasting overnight (reference period). In the test period, they took the same Zongertinib dose after 18 days of daily Carbamazepine pretreatment, with doses increasing from 200 mg to 600 mg. They continued taking 600 mg of Carbamazepine daily for 6 days after the Zongertinib dose.
Zongertinib Alone (Reference)/ Zongertinib+Carbamazepine (Test)	Carbamazepine	Participants took a single 60 mg oral dose of Zongertinib after fasting overnight (reference period). In the test period, they took the same Zongertinib dose after 18 days of daily Carbamazepine pretreatment, with doses increasing from 200 mg to 600 mg. They continued taking 600 mg of Carbamazepine daily for 6 days after the Zongertinib dose.

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	One hour before administration of zongertinib, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 11, 12, 24, 36, 48, 72, 120, and 168 hours after administration.	Area under the concentration-time curve of Zongertinib in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). 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.
Maximum Measured Concentration of Zongertinib in Plasma (Cmax)	One hour before administration of zongertinib, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 11, 12, 24, 36, 48, 72, 120, and 168 hours after administration.	Maximum measured concentration of Zongertinib in plasma (Cmax). 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.

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	One hour before administration of zongertinib, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 11, 12, 24, 36, 48, 72, 120, and 168 hours after administration.	Area under the concentration-time curve of Zongertinib in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). 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