Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the effect of BI 730357 under steady state conditions on the pharmacokinetics of digoxin, furosemide, metformin and rosuvastatin given as a cocktail (Reference, R: cocktail alone; Test T: cocktail given under steady state conditions of BI 730357).
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
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) * BMI of 18.5 to 29.9 kilogram per square meter (kg/m2) (inclusive) * Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation * Male subjects, or female subjects 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 adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device * Sexually abstinent * 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 units per liter (U/L) and estradiol below 30 nanograms per liter (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 millimetres of Mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (bpm) * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease assessed as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair) * Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders * During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection * further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of Digoxin in Plasma (Cmax, Digoxin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Maximum measured concentration of Digoxin in plasma is reported. The geometric mean is actually adjusted geometric mean. |
| Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Digoxin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Digoxin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean. |
| Maximum Measured Concentration of Metformin in Plasma (Cmax, Metformin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Maximum measured concentration of Metformin in plasma is reported. The geometric mean is actually adjusted geometric mean. |
| Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax, Rosuvastatin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Maximum measured concentration of Rosuvastatin in plasma is reported. The geometric mean is actually adjusted geometric mean. |
| Maximum Measured Concentration of Furosemide in Plasma (Cmax, Furosemide) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Maximum measured concentration of Furosemide in plasma is reported. The geometric mean is actually adjusted geometric mean. |
| Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Metformin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Metformin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean. |
| Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Rosuvastatin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Rosuvastatin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean. |
| Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Furosemide) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Furosemide in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Rosuvastatin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean. |
| Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Digoxin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Digoxin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean. |
| Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Furosemide) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Furosemide in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean. |
| Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Metformin) | 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2. | Area under the concentration-time curve of Metformin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean. |
Countries
Germany
Participant flow
Recruitment details
This open-label, non-randomised, 2-period fixed-sequence trial in healthy subjects was to test whether BI 730357 affects how 4 other medicines (rosuvastatin, digoxin, metformin, and furosemide) are taken up in the body.
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 |
|---|---|
| Cocktail (R) / BI 730357+Cocktail (T) Each subject participated in 2 treatment periods (Days -1 to 7 in period 1 and Days -7 to Day 8 in Period 2).
In period 1 (Visit 2): the cocktail reference treatment (R) consisting of 1 tablet of 0.25 milligrams (mg) of Digoxin, 0.1 milliliter (mL) oral solution of 1 mg Furosemide, 0.05 mL oral solution of 10 mg Metformin, and 1 film-coated tablet of 10 mg Rosuvastatin were taken orally, each medication as a single dose, once on Day 1 of period 1 (Visit 2).
In period 2 (Visit 3): 3 film-coated tablets of 100 mg BI 730357 were taken orally twice daily (bid) (daily dose 600 mg) from Day -7 until Day 6 of Visit 3 (13 days in total). On Day 1 of Visit 3, 1 hour after the morning dose of BI 730357, the cocktail (1 tablet of 0.25 mg of Digoxin, 0.1 mL oral solution of 1 mg Furosemide, 0.05 mL oral solution of 10 mg Metformin, and 1 film-coated tablet of 10 mg Rosuvastatin) 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 14 days. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 2 - BI 730357+Cocktail | COVID-19 related | 1 |
Baseline characteristics
| Characteristic | Cocktail (R) / BI 730357+Cocktail (T) |
|---|---|
| Age, Continuous | 34.2 Years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 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 | 15 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 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 / 15 | 0 / 15 | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 6 / 15 | 1 / 15 | 4 / 15 | 4 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 14 |
Outcome results
Primary
Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Digoxin)
Area under the concentration-time curve of Digoxin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Digoxin) | 13.34 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Digoxin) | 22.71 hour * nanomole / liter (h*nmol/L) |
90% CI: [143.73, 201.76]
Primary
Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Furosemide)
Area under the concentration-time curve of Furosemide in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Furosemide) | 157.57 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Furosemide) | 185.50 hour * nanomole / liter (h*nmol/L) |
90% CI: [110.57, 125.34]
Primary
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Metformin)
Area under the concentration-time curve of Metformin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Metformin) | 1460.83 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Metformin) | 1434.81 hour * nanomole / liter (h*nmol/L) |
90% CI: [94.89, 101.67]
Primary
Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Rosuvastatin)
Area under the concentration-time curve of Rosuvastatin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Rosuvastatin) | 90.08 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞, Rosuvastatin) | 110.87 hour * nanomole / liter (h*nmol/L) |
90% CI: [112.22, 134.98]
Primary
Maximum Measured Concentration of Digoxin in Plasma (Cmax, Digoxin)
Maximum measured concentration of Digoxin in plasma is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Maximum Measured Concentration of Digoxin in Plasma (Cmax, Digoxin) | 0.87 nanomole / liter (nmol/L) |
| Metformin + BI 730357 (Period 2) | Maximum Measured Concentration of Digoxin in Plasma (Cmax, Digoxin) | 1.40 nanomole / liter (nmol/L) |
90% CI: [129.17, 201.39]
Primary
Maximum Measured Concentration of Furosemide in Plasma (Cmax, Furosemide)
Maximum measured concentration of Furosemide in plasma is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Maximum Measured Concentration of Furosemide in Plasma (Cmax, Furosemide) | 51.03 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Maximum Measured Concentration of Furosemide in Plasma (Cmax, Furosemide) | 57.21 hour * nanomole / liter (h*nmol/L) |
90% CI: [101.26, 124.11]
Primary
Maximum Measured Concentration of Metformin in Plasma (Cmax, Metformin)
Maximum measured concentration of Metformin in plasma is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Maximum Measured Concentration of Metformin in Plasma (Cmax, Metformin) | 235.86 nanomole / liter (nmol/L) |
| Metformin + BI 730357 (Period 2) | Maximum Measured Concentration of Metformin in Plasma (Cmax, Metformin) | 215.63 nanomole / liter (nmol/L) |
90% CI: [88.04, 94.93]
Primary
Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax, Rosuvastatin)
Maximum measured concentration of Rosuvastatin in plasma is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax, Rosuvastatin) | 6.92 nanomole / liter (nmol/L) |
| Metformin + BI 730357 (Period 2) | Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax, Rosuvastatin) | 9.63 nanomole / liter (nmol/L) |
90% CI: [124.29, 155.51]
Secondary
Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Digoxin)
Area under the concentration-time curve of Digoxin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Digoxin) | 11.00 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Digoxin) | 19.11 hour * nanomole / liter (h*nmol/L) |
90% CI: [141.9, 212.8]
Secondary
Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Furosemide)
Area under the concentration-time curve of Furosemide in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Furosemide) | 151.01 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Furosemide) | 172.26 hour * nanomole / liter (h*nmol/L) |
90% CI: [107.93, 120.56]
Secondary
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Metformin)
Area under the concentration-time curve of Metformin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Metformin) | 1450.30 hour * nanomole / liter (h*nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Metformin) | 1424.70 hour * nanomole / liter (h*nmol/L) |
90% CI: [94.86, 101.73]
Secondary
Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Rosuvastatin)
Area under the concentration-time curve of Rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.
Time frame: 2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the Treated Set who provide 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. Thus, a subject is included in the PKS, even if he/she contributes only one PK parameter value for one period to the statistical assessment. Only those with non-missing results are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin (Period 1) | Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Rosuvastatin) | 78.83 hour * nanomole / liter (h * nmol/L) |
| Metformin + BI 730357 (Period 2) | Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Rosuvastatin) | 93.54 hour * nanomole / liter (h * nmol/L) |
90% CI: [108.83, 129.4]