Healthy
Conditions
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.
Interventions
DRUGzongertinib (C-14)
Oral solution
DRUGzongertinib
Film-coated tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 18.0 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. | 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). |
| Part B - Dose-normalised Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞,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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| 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. | 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. |
| 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. | Maximum measured concentration of zongertinib in plasma (Cmax) is reported. |
| 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) | 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. | 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. |
| 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. | 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. |
| 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. | Maximum measured concentration of \[14C\]-radioactivity (assessed by \[14C\]zongertinib-EQ) in plasma (Cmax) is reported. |
Countries
Netherlands
Participant flow
Recruitment details
Part A was an open-label, single-arm, single-dose part to investigate the pharmacokinetics of zongertinib and \[14C\]-radioactivity following one oral dose of zongertinib (C-14) containing a radioactive dose of approximately 3.7 Megabecquerel (MBq). Part B was an open-label, single-arm, single-period part to compare zongertinib administered orally to the intravenous infusion 2 hours later of zongertinib (C-14) solution (radioactive dose was approximately 0.03 MBq).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 8 |
| 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. | 7 |
| Total | 15 |
Baseline characteristics
| Characteristic | Part B - Zongertinib (T2), Then Zongertinib (C-14) (R) | Total | Part A - Zongertinib (C-14) (T1) |
|---|---|---|---|
| Age, Continuous | 29.3 Years STANDARD_DEVIATION 8.5 | 28.5 Years STANDARD_DEVIATION 8.4 | 27.8 Years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 15 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 | 1 Participants | 1 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 | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 7 / 8 | 2 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
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).
Time frame: 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.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) restricted to Part A included all part A subjects in the TS who provided at least one 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 | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | 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) | feurine, 0-tz | 1.30 Percentage of the administered dose | Geometric Coefficient of Variation 16.8 |
| Part A - Zongertinib (C-14) (T1) | 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) | fefaeces, 0-tz | 92.5 Percentage of the administered dose | Geometric Coefficient of Variation 3.66 |
| Part A - Zongertinib (C-14) (T1) | 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) | feurine + fefaeces, 0-tz | 93.8 Percentage of the administered dose | Geometric Coefficient of Variation 3.62 |
Primary
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.
Time frame: 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.
Population: PKS restricted to Part B included all part B subjects in the TS who provided at least one 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 | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | Part B - Dose-normalised Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞,Norm) | zongertinib | 223.39 hour*millimole/Liter/kilogram |
| Part A - Zongertinib (C-14) (T1) | Part B - Dose-normalised Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞,Norm) | [14C]zongertinib | 293.26 hour*millimole/Liter/kilogram |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [70.21, 82.65]
Secondary
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.
Time frame: 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.
Population: PKS restricted to Part A included all part A subjects in the TS who provided at least one 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) | Dispersion |
|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | 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) | 23700 hour*nanomole/Liter | Geometric Coefficient of Variation 17.3 |
Secondary
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.
Time frame: 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.
Population: PKS restricted to Part A included all part A subjects in the TS who provided at least one 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) | Dispersion |
|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | 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) | 14100 hour*nanomole/Liter | Geometric Coefficient of Variation 14 |
Secondary
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.
Time frame: 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.
Population: PKS restricted to Part A included all part A subjects in the TS who provided at least one 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) | Dispersion |
|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | Part A - Maximum Measured Concentration of [14C]-Radioactivity (Assessed by [14C]Zongertinib-EQ) in Plasma (Cmax) | 1450 nanomole/Liter | Geometric Coefficient of Variation 18.8 |
Secondary
Part A - Maximum Measured Concentration of Zongertinib in Plasma (Cmax)
Maximum measured concentration of zongertinib in plasma (Cmax) is reported.
Time frame: 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.
Population: PKS restricted to Part A included all part A subjects in the TS who provided at least one 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) | Dispersion |
|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | Part A - Maximum Measured Concentration of Zongertinib in Plasma (Cmax) | 1160 nanomole/Liter | Geometric Coefficient of Variation 17.2 |
Secondary
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.
Time frame: 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.
Population: PKS restricted to Part B included all part B subjects in the TS who provided at least one 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 | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | 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) | zongertinib | 219.72 hour*millimole/Liter/kilogram |
| Part A - Zongertinib (C-14) (T1) | 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) | [14C]zongertinib | 285.38 hour*millimole/Liter/kilogram |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [70.92, 83.59]
Secondary
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.
Time frame: 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.
Population: PKS restricted to Part B included all part B subjects in the TS who provided at least one 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 | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A - Zongertinib (C-14) (T1) | Part B - Dose-normalised Maximum Measured Concentration in Plasma (Cmax,Norm) | zongertinib | 16.57 picomole/Liter/microgram |
| Part A - Zongertinib (C-14) (T1) | Part B - Dose-normalised Maximum Measured Concentration in Plasma (Cmax,Norm) | [14C]zongertinib | 63.50 picomole/Liter/microgram |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [22.12, 30.79]