Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the relative bioavailability of a single dose of BI 1810631 intended commercial formulation (iCF) under fed (Test treatment, T) and fasted (Reference treatment, R) conditions.
Interventions
DRUGzongertinib
Participants received a single oral dose of 240 mg Zongertinib (4 x 60 mg tablets) in two periods: in Period 1 after an overnight fast of at least 10 hours, and in Period 2 following a high fat/high calorie meal.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
two-way crossover
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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 18.5 to 29.9 kg/m2 (inclusive) 4. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
Exclusion criteria
1. Any finding in the medical examination (including Blood pressure (BP), pulse rate (PR) or electrocardiogram (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 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours before Zongertinib administration, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours following 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 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. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint. |
| Maximum Measured Concentration of the Zongertinib in Plasma (Cmax) | Within 3 hours before Zongertinib administration, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours following administration. | Maximum measured concentration of Zongertinib in plasma (Cmax). Geometric least square mean (adjusted geometric mean) and 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. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours before Zongertinib administration, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours following 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 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. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint. |
Countries
Germany
Participant flow
Recruitment details
This was an open-label, randomized, two-way crossover design trial. Healthy males received a single oral dose of 240 mg Zongertinib (BI 1810631) in its intended commercial formulation (iCF) following an overnight fast and after a standardized high-calorie, high-fat meal. There was a washout period of 14 days between doses. The primary objective was to evaluate how Zongertinib is absorbed when taken with and without food, to determine differences in its bioavailability between these states.
Pre-assignment details
All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that they (the participants) strictly met all inclusion and none of the exclusion criteria. Participants were not to be allocated to a treatment sequence if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Zongertinib iCF Fasted (Reference (R)) /Zongertinib iCF Fed (Test (T)) Two period crossover separated by a wash-out of at least 14 days:
Period 1: Participants received a single oral dose of 240 milligram (mg) of Zongertinib as film coated tablets (4x 60 mg tablets) following an overnight fast of at least 10 hours.
Period 2: Participants received a single oral dose of 240 milligram (mg) Zongertinib as film coated tablets (4x 60 mg tablet) following a high fat/high calorie meal. | 8 |
| Zongertinib iCF Fed (Test (T)) / Zongertinib iCF Fasted (Reference (R)) Two period crossover separated by a wash-out of at least 14 days:
Period 1: Participants received a single oral dose of 240 milligram (mg) Zongertinib as film coated tablets (4x 60 mg tablet) following a high fat/high calorie meal.
Period 2: Participants received a single oral dose of 240 milligram (mg) of Zongertinib as film coated tablets (4x 60 mg tablets) following an overnight fast of at least 10 hours. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Zongertinib iCF Fed (Test (T)) / Zongertinib iCF Fasted (Reference (R)) | Total | Zongertinib iCF Fasted (Reference (R)) /Zongertinib iCF Fed (Test (T)) |
|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 11.2 | 47.9 years STANDARD_DEVIATION 8.9 | 50.0 years STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 16 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 16 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 7 / 16 | 7 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
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 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. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint.
Time frame: Within 3 hours before Zongertinib administration, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours following administration.
Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were randomised and received at least one dose of trial medication and who provided at least one pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Zongertinib iCF Fed (Test (T)) | Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 59457.92 hour*nanomol/Liter (h*nmol/L) |
| Zongertinib iCF Fasted (Reference (R)) | Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 46951.21 hour*nanomol/Liter (h*nmol/L) |
Comparison: Relative bioavailability of Zongertinib administered in fed state (Test) compared with Zongertinib administered in fasted state (Reference) was estimated by the ratios of the gMeans (Test/Reference). Their corresponding 2-sided 90% confidence intervals (CIs) were provided. This method corresponds to 2 one-sided t-test procedures, each at the 5% significance level.90% CI: [112.09, 143.08]
Primary
Maximum Measured Concentration of the Zongertinib in Plasma (Cmax)
Maximum measured concentration of Zongertinib in plasma (Cmax). Geometric least square mean (adjusted geometric mean) and 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. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint.
Time frame: Within 3 hours before Zongertinib administration, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours following administration.
Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were randomised and received at least one dose of trial medication and who provided at least one pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Zongertinib iCF Fed (Test (T)) | Maximum Measured Concentration of the Zongertinib in Plasma (Cmax) | 4666.87 nanomol/Liter (nmol/L) |
| Zongertinib iCF Fasted (Reference (R)) | Maximum Measured Concentration of the Zongertinib in Plasma (Cmax) | 3700.37 nanomol/Liter (nmol/L) |
Comparison: Relative bioavailability of Zongertinib administered in fed state (Test) compared with Zongertinib administered in fasted state (Reference) was estimated by the ratios of the gMeans (Test/Reference). Their corresponding 2-sided 90% confidence intervals (CIs) were provided. This method corresponds to 2 one-sided t-test procedures, each at the 5% significance level.90% CI: [106.34, 149.58]
Secondary
Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
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 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. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint.
Time frame: Within 3 hours before Zongertinib administration, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours following administration.
Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were randomised and received at least one dose of trial medication and who provided at least one pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Zongertinib iCF Fed (Test (T)) | Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 59986.25 hour*nanomol/Liter (h*nmol/L) |
| Zongertinib iCF Fasted (Reference (R)) | Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 47594.57 hour*nanomol/Liter (h*nmol/L) |
Comparison: Relative bioavailability of Zongertinib administered in fed state (Test) compared with Zongertinib administered in fasted state (Reference) was estimated by the ratios of the gMeans (Test/Reference). Their corresponding 2-sided 90% confidence intervals (CIs) were provided. This method corresponds to 2 one-sided t-test procedures, each at the 5% significance level.90% CI: [111.7, 142.21]