Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the absolute bioavailability of BI 1467335 with an intravenous microdose formulation containing labelled \[C-14\] BI 1467335 and an unlabelled oral tablet formulation of BI 1467335 in healthy male subjects. The secondary objective is the evaluation of additional pharmacokinetic parameters following the two treatments.
Interventions
DRUGBI 1467335
Film-coated tablet
DRUGBI 1467335 (C-14) intravenous solution
Intravenous solution
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the investigator's assessment, 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 65 years (incl.) * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.) * Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation * Subjects who are sexually active must use, with their partner, highly effective contraception from the time of administration of trial medication until 4 months after administration of trial medication. Adequate methods are: * Condoms plus use of hormonal contraception by the female partner that started at least 2 months prior to administration of trial medication (e.g., implants, injectables, combined oral or vaginal contraceptives, intrauterine device) or * Condoms plus surgical sterilization (vasectomy at least 1 year prior to enrolment) or * Condoms plus surgically sterilised partner (including hysterectomy) or * Condoms plus intrauterine device or * Condoms plus partner of non-childbearing potential (including homosexual men) study drug via seminal fluid Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, with their partner, they must comply with the contraceptive requirements detailed above
Exclusion criteria
* Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease judged as clinically relevant by the investigator * Clinically significant gastrointestinal, hepatic, renal, respiratory (including but not limited to interstitial lung disease), cardiovascular, metabolic, immunological or hormonal disorders * Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and 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 * Chronic or relevant acute infections * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Within 30 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval * Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug * Smoker (more than 5 cigarettes or 1 cigar or 1 pipe per day) * Inability to refrain from smoking on specified trial days * Average intake of more than 24 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)e the reference range that the investigator considers to be of clinical relevance * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial * Inability to comply with dietary regimen of trial site * A marked baseline prolongation of QT/QTc interval (such as QTcF intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening * A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| After the First Dose: Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1 | Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake. | After the first dose: Area under the concentration-time curve of BI 1467335 over the time interval from 0 extrapolated to infinity (AUC0-infinity) of BI 1467335 (after oral administration) and \[C-14\] BI 1467335 (after iv administration) on Day 1 is presented. Standard Error is actually a geometric standard Error in method of dispersion. Pharmacokinetic samples were collected on Day 1 for both groups. |
| After the First Dose: Maximum Measured Concentration of the BI 1467335 in Plasma (Cmax ) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1 | Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake. | After the first dose: maximum measured concentration of BI 1467335 in plasma (Cmax ) of BI 1467335 (after oral administration) and \[C-14\] BI 1467335 (after iv administration) on Day 1 is presented. Pharmacokinetic samples were collected on Day 1 for both groups. |
| Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (AUC 0-infinity, 28) | 5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake. | After the multiple doses Area under the concentration-time curve of the BI 1467335 over the time interval from 0 extrapolated to 24 h after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 28 (AUC 0-infinity, 28) is presented. Standard Error is actually a geometric standard Error in method of dispersion. Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details. |
| After Multiple Doses: Maximum Measured Concentration of BI 1467335 in Plasma of BI 1467335 After Oral Administration and [C-14] BI 1467335 After Intravenous Administration on Day 28 (Cmax, 28) | 5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake. | After multiple doses: maximum measured concentration of the analyte in plasma of BI 1467335 after oral administration and \[C-14\] BI 1467335 after intravenous administration on Day 28 (Cmax, 28) is presented. Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (CL) | Pharmacokinetic samples were taken 2 h pre-dose and at 1.083, 1.25, 1.417, 1.583, 1.75, 2 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after last drug administration on day 1 for [C-14] BI 1467335. | Clearance of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 1 (CL). |
| Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (CL28) | Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28. | Clearance of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 28 (CL28). |
| Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (Vz) | Pharmacokinetic samples were taken 2 h pre-dose and at 1.083, 1.25, 1.417, 1.583, 1.75, 2 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after last drug administration on day 1 for [C-14] BI 1467335. | Volume of distribution of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 1 (Vz). |
| Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (Tmax) | Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake. | Time from dosing to the maximum measured concentration of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 1 (tmax). Pharmacokinetic samples were collected on Day 1 for both groups. |
| Absolute Bioavailability (Fabs) of BI 1467335 After Oral Administration on Day 1 | Pharmacokinetic samples were taken 2 h pre-dose and at 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after last drug administration on day 1 for BI 1467335. | Absolute bioavailability (Fabs) of BI 1467335 after oral administration on Day 1, F (absolute bioavailability) on Day 1 determined as ratio Day 1 (AUC 0-∞/Dose)oral/ (AUC0-∞/Dose)iv·100 per subject. |
| Absolute Bioavailability of BI 1467335 After Oral Administration on Day 28 (Fabs,28) | Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28. | Absolute bioavailability of BI 1467335 after oral administration on Day 28 (Fabs,28), F (absolute bioavailability) on Day 28 determined as ratio Day 28 (AUC 0-∞/Dose)oral/ (AUC0-∞/Dose)iv·100 per subject. |
| Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (Vz, 28) | Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28. | Volume of distribution of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 28 (Vz, 28). |
| Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (Tmax,28) | 5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake. | Time from dosing to the maximum measured concentration of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 28 (tmax,28). Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details. |
| Observed Terminal Half-life of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (t1/2) | Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake. | Observed terminal half-life of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 1 (t1/2). Pharmacokinetic samples were collected on Day 1 for both groups. |
| Observed Terminal Half-life of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (t1/2,28) | Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28. | Observed terminal half-life of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 28 (t1/2,28). |
Countries
Netherlands
Participant flow
Recruitment details
This was an open-label, non-randomized, single arm, multiple dose design trial in healthy male participants received unlabelled oral doses of BI 1467335 (Test product 1 (T1), film coated tablet) for 28 days and in addition microtracer-radiolabelled BI 1467335 as intravenous (iv) infusions on Days 1 and 28 (Test product 2 (T2)).
Pre-assignment details
All participants were screened for eligibility to participate in the study. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| BI 1467335 All participants were orally administered treatment T1 consisted of 10 milligram (mg) (2x5) film-coated tablets of BI 1467335 once daily for 28 days in the fasted state with about 240 milliliters (ml) of non-sparkling water. In addition subjects also received the two single 10 ml intravenous (iv) infusion comprised 50 microgram (μg) BI 1467335 free base, consisting a mixture of 41.15 μg unlabelled BI 1467335 and 8.85 μg \[C-14\] BI 1467335 on Day 1 and a mixture of 45 μg unlabelled BI 1467335 and 5 μg \[C-14\] BI 1467335 free base on Day 28. The infusion started 1 hour after the intake of the BI 1467335 film-coated tablets on Day 1 and Day 28 and ended 15 minutes later. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | BI 1467335 |
|---|---|
| Age, Continuous | 37.3 Years STANDARD_DEVIATION 16.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
After Multiple Doses: Maximum Measured Concentration of BI 1467335 in Plasma of BI 1467335 After Oral Administration and [C-14] BI 1467335 After Intravenous Administration on Day 28 (Cmax, 28)
After multiple doses: maximum measured concentration of the analyte in plasma of BI 1467335 after oral administration and \[C-14\] BI 1467335 after intravenous administration on Day 28 (Cmax, 28) is presented. Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details.
Time frame: 5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | After Multiple Doses: Maximum Measured Concentration of BI 1467335 in Plasma of BI 1467335 After Oral Administration and [C-14] BI 1467335 After Intravenous Administration on Day 28 (Cmax, 28) | 92.5 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 42.8 |
| BI 1467335 (C-14) iv | After Multiple Doses: Maximum Measured Concentration of BI 1467335 in Plasma of BI 1467335 After Oral Administration and [C-14] BI 1467335 After Intravenous Administration on Day 28 (Cmax, 28) | 0.290 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 19.5 |
Primary
After the First Dose: Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1
After the first dose: Area under the concentration-time curve of BI 1467335 over the time interval from 0 extrapolated to infinity (AUC0-infinity) of BI 1467335 (after oral administration) and \[C-14\] BI 1467335 (after iv administration) on Day 1 is presented. Standard Error is actually a geometric standard Error in method of dispersion. Pharmacokinetic samples were collected on Day 1 for both groups.
Time frame: Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
Population: Pharmacokinetic (PK) set (PKS): All subjects in the TS who provided at least one primary PK parameter not excluded due to a protocol violation relevant to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | After the First Dose: Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1 | 0.35 millimole * hour/ Liter/ kilogram | Standard Error 1.25 |
| BI 1467335 (C-14) iv | After the First Dose: Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1 | 4.16 millimole * hour/ Liter/ kilogram | Standard Error 1.25 |
Comparison: The statistical model used for the analysis of the primary PK endpoints was an ANOVA (analysis of variance) model on the logarithmic scale. The model included effects accounting for 'subject' and 'formulation' as sources of variation; 'subject' was considered as a random effect, whereas 'formulation' was considered as a fixed effect.90% CI: [5.88, 11.82]ANOVA
Primary
After the First Dose: Maximum Measured Concentration of the BI 1467335 in Plasma (Cmax ) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1
After the first dose: maximum measured concentration of BI 1467335 in plasma (Cmax ) of BI 1467335 (after oral administration) and \[C-14\] BI 1467335 (after iv administration) on Day 1 is presented. Pharmacokinetic samples were collected on Day 1 for both groups.
Time frame: Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | After the First Dose: Maximum Measured Concentration of the BI 1467335 in Plasma (Cmax ) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1 | 2.72 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 105 |
| BI 1467335 (C-14) iv | After the First Dose: Maximum Measured Concentration of the BI 1467335 in Plasma (Cmax ) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1 | 0.152 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 87.6 |
Primary
Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (AUC 0-infinity, 28)
After the multiple doses Area under the concentration-time curve of the BI 1467335 over the time interval from 0 extrapolated to 24 h after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 28 (AUC 0-infinity, 28) is presented. Standard Error is actually a geometric standard Error in method of dispersion. Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details.
Time frame: 5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (AUC 0-infinity, 28) | 37.38 millimole*hour/ Liter/ kilogram | Standard Error 1.24 |
| BI 1467335 (C-14) iv | Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (AUC 0-infinity, 28) | 60.16 millimole*hour/ Liter/ kilogram | Standard Error 1.24 |
Comparison: The statistical model used for the analysis of the primary PK endpoints was an ANOVA (analysis of variance) model on the logarithmic scale. The model included effects accounting for 'subject' and 'formulation' as sources of variation; 'subject' was considered as a random effect, whereas 'formulation' was considered as a fixed effect.90% CI: [52.08, 74.14]ANOVA
Secondary
Absolute Bioavailability (Fabs) of BI 1467335 After Oral Administration on Day 1
Absolute bioavailability (Fabs) of BI 1467335 after oral administration on Day 1, F (absolute bioavailability) on Day 1 determined as ratio Day 1 (AUC 0-∞/Dose)oral/ (AUC0-∞/Dose)iv·100 per subject.
Time frame: Pharmacokinetic samples were taken 2 h pre-dose and at 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after last drug administration on day 1 for BI 1467335.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | Absolute Bioavailability (Fabs) of BI 1467335 After Oral Administration on Day 1 | 0.0834 Ratio | Geometric Coefficient of Variation 75.9 |
Secondary
Absolute Bioavailability of BI 1467335 After Oral Administration on Day 28 (Fabs,28)
Absolute bioavailability of BI 1467335 after oral administration on Day 28 (Fabs,28), F (absolute bioavailability) on Day 28 determined as ratio Day 28 (AUC 0-∞/Dose)oral/ (AUC0-∞/Dose)iv·100 per subject.
Time frame: Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | Absolute Bioavailability of BI 1467335 After Oral Administration on Day 28 (Fabs,28) | 0.621 Ratio | Geometric Coefficient of Variation 35.1 |
Secondary
Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (CL)
Clearance of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 1 (CL).
Time frame: Pharmacokinetic samples were taken 2 h pre-dose and at 1.083, 1.25, 1.417, 1.583, 1.75, 2 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after last drug administration on day 1 for [C-14] BI 1467335.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (CL) | 14300.0 millilitre/minute (mL/min) | Geometric Coefficient of Variation 87.2 |
Secondary
Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (CL28)
Clearance of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 28 (CL28).
Time frame: Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (CL28) | 988 millilitre/minute (mL/min) | Geometric Coefficient of Variation 66 |
Secondary
Observed Terminal Half-life of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (t1/2)
Observed terminal half-life of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 1 (t1/2). Pharmacokinetic samples were collected on Day 1 for both groups.
Time frame: Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 1467335 Tab | Observed Terminal Half-life of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (t1/2) | 0.751 Hours (h) |
| BI 1467335 (C-14) iv | Observed Terminal Half-life of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (t1/2) | 0.341 Hours (h) |
Secondary
Observed Terminal Half-life of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (t1/2,28)
Observed terminal half-life of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 28 (t1/2,28).
Time frame: Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 1467335 Tab | Observed Terminal Half-life of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (t1/2,28) | 2.43 Hours (h) |
Secondary
Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (Tmax)
Time from dosing to the maximum measured concentration of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 1 (tmax). Pharmacokinetic samples were collected on Day 1 for both groups.
Time frame: Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 1467335 Tab | Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (Tmax) | 1.08 Hours (h) |
| BI 1467335 (C-14) iv | Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (Tmax) | 0.250 Hours (h) |
Secondary
Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (Tmax,28)
Time from dosing to the maximum measured concentration of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of \[C-14\] BI 1467335 on Day 28 (tmax,28). Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details.
Time frame: 5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake.
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 1467335 Tab | Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (Tmax,28) | 1.08 Hours (h) |
| BI 1467335 (C-14) iv | Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (Tmax,28) | 0.250 Hours (h) |
Secondary
Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (Vz)
Volume of distribution of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 1 (Vz).
Time frame: Pharmacokinetic samples were taken 2 h pre-dose and at 1.083, 1.25, 1.417, 1.583, 1.75, 2 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after last drug administration on day 1 for [C-14] BI 1467335.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (Vz) | 554 Liter (L) | Geometric Coefficient of Variation 128 |
Secondary
Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (Vz, 28)
Volume of distribution of the analyte \[C-14\] BI 1467335 after intravenous administration on Day 28 (Vz, 28).
Time frame: Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1467335 Tab | Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (Vz, 28) | 204 Liter (L) | Geometric Coefficient of Variation 13.4 |