Healthy
Conditions
Brief summary
The trial will be performed to assess the influence of BI 730357 on the pharmacokinetics of caffeine, warfarin, omeprazole and midazolam.
Interventions
DRUGPercoffedrinol®
Tablet
DRUGCoumadin®
Tablet
DRUGAntra MUPS®
Gastro-resistant tablet
DRUGMidazolam-ratiopharm®
Oral solution
DRUGBI 730357
Film-coated tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Two Periods (Period 1 and Period 2) for each participant.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy 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 prior to admission to the study, in accordance with GCP and local legislation * Either male subject, or female subject who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion: * Use of non-hormonal intrauterine device plus condom for birth control * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) * Surgically sterilised (including hysterectomy or bilateral tubal occlusion) * Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)
Exclusion criteria
* 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 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 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 (except appendectomy or simple hernia repair) that could interfere with the pharmacokinetics (PK) of the trial medication * 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 inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods. | Area under the concentration-time curve of caffeine in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, caffeine) is reported. |
| Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods. | Maximum measured concentration of the caffeine in plasma (Cmax, caffeine) is reported. |
| Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods. | Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Area under the concentration-time curve of S-warfarin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity,S-warfain) is reported. |
| Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods. | Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Maximum measured concentration of the S-warfarin in plasma (Cmax) is reported. |
| Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods. | Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, omeprazole) is reported. |
| Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods. | Maximum measured concentration of omeprazole in plasma (Cmax, omeprazole) is reported. |
| Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods. | Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, midazolam) is reported. |
| Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam) | Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods. | Maximum measured concentration of midazolam in plasma (Cmax, midazolam) is reported. |
Countries
Germany
Participant flow
Recruitment details
This was a phase 1, non-randomised, open-label, 2-treatment, 2-period fixed sequence design trial in healthy people to test whether BI 730357 influences the amount of caffeine, warfarin, omeprazole, and midazolam in the blood.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist 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 |
|---|---|
| Drug Cocktail Alone (R) Then Drug Cocktail + BI 730357 (T) In period 1: Participants were administered the cocktail reference treatment (R) consisting of 2 tablets of 50 milligrams (mg) (total dose 100mg) of caffeine (Percoffedrinol® N 50 mg Tablets), 2 tablets of 5 mg (total dose 10 mg) of warfarin sodium (Coumadin® 5 mg), 1 tablet of 20 mg of omeprazole (Antra MUPS® 20 mg gastro-resistant tablet), and 1 milliliter (mL) oral solution of 2 mg of midazolam (Midazolam-ratiopharm® 2 mg/mL oral solution), each medication as a single dose, once on Day 1 of period 1 (Visit 2).
In period 2 (Visit 3): Participants were administered 3 film-coated tablets of 100 mg BI 730357 orally twice daily (bid) (daily dose 600 mg) from Day -14 to Day 6 of Visit 3 (20 days in total). On the 15th day of BI 730357 treatment (Day 1 of Visit 3, 1 h after the morning dose of BI 730357), the cocktail (100 mg caffeine, 10 mg warfarin, 20 mg omeprazole, and 2 mg midazolam) was administered orally once. The BI 730357+ cocktail was the test treatment (T).
The two cocktail administrations were separated by a wash-out period of at least 20 days. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Drug Cocktail Alone (R) Then Drug Cocktail + BI 730357 (T) |
|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 16 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 3 / 16 | 2 / 16 | 0 / 16 | 2 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine)
Area under the concentration-time curve of caffeine in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, caffeine) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine) | 84569.29 hours *nanomole/Liter (h*nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine) | 94764.64 hours *nanomole/Liter (h*nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [101.02, 124.3]
Primary
Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam)
Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, midazolam) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam) | 56.81 hours * nanomole/Liter (h*nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam) | 72.07 hours * nanomole/Liter (h*nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [119.15, 135.05]
Primary
Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole)
Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, omeprazole) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole) | 933.62 hours * nanomole/Liter (h*nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole) | 931.22 hours * nanomole/Liter (h*nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [89.66, 110.95]
Primary
Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin)
Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Area under the concentration-time curve of S-warfarin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity,S-warfain) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin) | 55770.25 hours * nanomole/Liter (h*nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin) | 61559.60 hours * nanomole/Liter (h*nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [107.15, 113.71]
Primary
Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam)
Maximum measured concentration of midazolam in plasma (Cmax, midazolam) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam) | 19.09 nanomole/Liter (nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam) | 24.87 nanomole/Liter (nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [121.25, 139.92]
Primary
Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole)
Maximum measured concentration of omeprazole in plasma (Cmax, omeprazole) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole) | 504.07 nanomole/Liter (nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole) | 359.50 nanomole/Liter (nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [44.64, 113.96]
Primary
Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine)
Maximum measured concentration of the caffeine in plasma (Cmax, caffeine) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine) | 11973.25 nanomole/Liter (nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine) | 11583.25 nanomole/Liter (nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [91.55, 102.23]
Primary
Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin)
Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Maximum measured concentration of the S-warfarin in plasma (Cmax) is reported.
Time frame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was defined as primary and was not excluded due to a clinical trial protocol (CTP) deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if the subject contributed only 1 PK parameter value for 1 period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Caffeine (Reference (R)) | Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin) | 1622.94 nanomole/Liter (nmol/L) |
| BI 730357 + Caffeine (Test (T)) | Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin) | 1760.38 nanomole/Liter (nmol/L) |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model. These quantities were then back-transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. This model included effects accounting for the following sources of variation: subjects (random effect) and treatment (fixed effect).90% CI: [104.11, 113.01]