Healthy
Conditions
Brief summary
Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 137882 in Healthy Male Volunteers
Detailed description
As a transition from preclinical investigations to clinical development in this first-in-man trial, safety, tolerability, and pharmacokinetics of BI 137882 will be assessed in healthy male volunteers using single rising oral doses in order to provide the basis for a potential ongoing clinical development of BI 137882 in the indication of COPD. Healthy male subjects aged 21 - 50 years will be recruited for this study. They provide a relatively stable physiological, biochemical and hormonal basis (steady state) for studying drug effects, they show no disease-related variation and they are not taking concomitant medication. Within each dose group, all actively treated individuals will receive the same BI 137882 dose. The next higher dose will only be administered if the treatment in the preceding dose group was safe and well tolerated.
Interventions
DRUGBI 137882
Powder for oral solution
DRUGPlacebo
Powder for oral solution
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
MALE
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests 2. Age 21 to 50 years 3. BMI 18.5 to 29.9 kg/m2 (Body Mass Index) 4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
Exclusion criteria
1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. Surgery of the gastrointestinal tract (except appendectomy) 5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders 6. History of relevant orthostatic hypotension, fainting spells or blackouts. 7. Chronic or relevant acute infections 8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 9. Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial 10. Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial 11. Participation in another trial with an investigational drug within two months prior to administration or during the trial 12. Smoker (more than 10 cigarettes /day) 13. Inability to refrain from smoking on trial days 14. Alcohol abuse (more than 20 g/day) 15. Drug abuse 16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial) 17. Excessive physical activities (within one week prior to administration or during the trial) 18. Any laboratory value outside the reference range that is of clinical relevance 19. Inability to comply with dietary regimen of trial site 20. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms); 21. A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Drug Related Adverse Events | From baseline up to 28 days | Number of subjects with drug related adverse events (AEs) |
| Blood Pressure | Baseline and 28 days | Change from baseline for systolic blood pressure (SBP) and diastolic blood pressure (DBP) |
| Pulse Rate (PR) | Baseline and 28 days | Change from Baseline to 28 Days in Pulse Rate |
| Respiratory Rate (RR) | Baseline and 28 days | Change from Baseline to 28 Days in Respiratory rate (RR) |
| Body Temperature | Baseline and 28 days | Change from baseline to 28 Days in Body temperature |
| Assessment of Tolerability by Investigator | 28 days | The investigator assessed tolerability based on adverse events and the laboratory evaluation according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Residence Time (MRTpo) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Mean residence time of the analyte in the body after oral administration. |
| Apparent Clearance (CL/F) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Apparent clearance of the analyte in plasma after extravascular administration. |
| Apparent Volume of Distribution (Vz/F) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Apparent volume of distribution of the analyte during the terminal phase. |
| Amount of BI 137882 Eliminated in Urine From the Time Point t1 to Time Point t2 | 0-4, 4-8, 8-12, and 12-24 hours after drug administration | Amount of BI 137882 eliminated in urine from the time point t1 to time point t2 (Aet1-t2) |
| Fraction of BI 137882 Eliminated in Urine From Time Point t1 to Time Point t2 | 0-4, 4-8, 8-12, and 12-24 hours after drug administration | Fraction of BI 137882 eliminated in urine from time point t1 to time point t2 (fet1-t2) |
| Maximum Measured Concentration (Cmax) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Maximum measured concentration of BI 137882 in plasma. |
| Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration | Concentrations of TNF-α in plasma were determined by an enzyme-linked immunosorbent assay (ELISA). Concentrations of TNF-α in blood drawn after treatment with BI 137882 were compared with those in pre-dose samples to calculate the percent of inhibition of LPS induction of TNF-α production. Results indicate percent change from baseline of LPS-induced TNF-α production. A positive value indicates inhibition of the production. |
| Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration | Percent of inhibition of fMLP induction of LTB4 production. Concentrations of LTB4 in plasma were determined by an enzyme-linked immunosorbent assay (ELISA). Results indicate percent change from baseline of fMLP induction of LTB4 production. A positive value indicates inhibition of the production. |
| Area Under the Effect Curve (AUEC) | 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration | Area under the effect curve for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-α/LTB4 production. A positive value indicates inhibition of the production. |
| Maximum Effect (Emax) | 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration | Maximum effect for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-α/LTB4 production. A positive value indicates inhibition of the production. |
| Minimum Effect (Emin) | 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration | Minimum effect for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-α/LTB4 production. A positive value indicates inhibition of the production. |
| Renal Clearance of BI 137882 From the Time Point t1 Until the Time Point t2 | 0-4, 4-8, 8-12, and 12-24 hours after drug administration | Renal clearance of BI 137882 from the time point t1 until the time point t2 (CLR,t1-t2) |
| Time to Maximum Measured Concentration (Tmax) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Time from dosing to maximum measured concentration of the analyte in plasma. |
| Area Under the Curve 0 to Infinity (AUC0-infinity) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Area under the concentration-time curve of BI 137882 in plasma over the time interval from 0 extrapolated to infinity. |
| Terminal Half-life (t1/2) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Terminal half-life of BI 137882 in plasma. |
| Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point. |
| Terminal Rate Constant (λz) | 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration | Terminal rate constant in plasma. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo A solution of 0.7% SDS and volume depends on corresponding dose group | 10 |
| 0.01 mg BI 137882 with 0.01 mg Dose level | 5 |
| 0.03 mg BI 137882 with 0.03 mg Dose level | 6 |
| 0.1 mg BI 137882 with 0.1 mg Dose level | 6 |
| 0.25 mg BI 137882 with 0.25 mg Dose level | 6 |
| 0.5 mg BI 137882 with 0.5 mg Dose level | 1 |
| 0.6 mg BI 137882 with 0.6 mg Dose level | 6 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | 0.01 mg | Placebo | 0.03 mg | 0.1 mg | 0.25 mg | 0.5 mg | 0.6 mg |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 36.8 Years STANDARD_DEVIATION 7.9 | 34.8 Years STANDARD_DEVIATION 10.3 | 35.7 Years STANDARD_DEVIATION 7.6 | 40.8 Years STANDARD_DEVIATION 6.6 | 37.2 Years STANDARD_DEVIATION 7.1 | 36.5 Years STANDARD_DEVIATION 10 | 42.0 Years | 35.5 Years STANDARD_DEVIATION 8.5 |
| Alcohol Status Drinks - no interference | 38 participants | 5 participants | 9 participants | 6 participants | 6 participants | 6 participants | 1 participants | 5 participants |
| Alcohol Status Drinks - possible interference | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Alcohol Status Never Drinker | 2 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 5 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 1 Participants | 6 Participants |
| Smoking Status Currently Smokes | 10 participants | 1 participants | 5 participants | 0 participants | 1 participants | 1 participants | 0 participants | 2 participants |
| Smoking Status Ex-Smoker | 8 participants | 2 participants | 3 participants | 1 participants | 0 participants | 2 participants | 0 participants | 0 participants |
| Smoking Status Never Smoked | 22 participants | 2 participants | 2 participants | 5 participants | 5 participants | 3 participants | 1 participants | 4 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 10 | 1 / 5 | 5 / 6 | 5 / 6 | 5 / 6 | 1 / 1 | 1 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 1 | 0 / 6 |
Outcome results
Primary
Assessment of Tolerability by Investigator
The investigator assessed tolerability based on adverse events and the laboratory evaluation according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'.
Time frame: 28 days
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Assessment of Tolerability by Investigator | Not assessable | 0 Participants |
| Placebo | Assessment of Tolerability by Investigator | Not satisfactory | 0 Participants |
| Placebo | Assessment of Tolerability by Investigator | Satisfactory | 0 Participants |
| Placebo | Assessment of Tolerability by Investigator | Bad | 0 Participants |
| Placebo | Assessment of Tolerability by Investigator | Good | 10 Participants |
| 0.01 mg | Assessment of Tolerability by Investigator | Satisfactory | 0 Participants |
| 0.01 mg | Assessment of Tolerability by Investigator | Good | 5 Participants |
| 0.01 mg | Assessment of Tolerability by Investigator | Bad | 0 Participants |
| 0.01 mg | Assessment of Tolerability by Investigator | Not satisfactory | 0 Participants |
| 0.01 mg | Assessment of Tolerability by Investigator | Not assessable | 0 Participants |
| 0.03 mg | Assessment of Tolerability by Investigator | Satisfactory | 1 Participants |
| 0.03 mg | Assessment of Tolerability by Investigator | Not satisfactory | 0 Participants |
| 0.03 mg | Assessment of Tolerability by Investigator | Bad | 0 Participants |
| 0.03 mg | Assessment of Tolerability by Investigator | Good | 5 Participants |
| 0.03 mg | Assessment of Tolerability by Investigator | Not assessable | 0 Participants |
| 0.1 mg | Assessment of Tolerability by Investigator | Good | 6 Participants |
| 0.1 mg | Assessment of Tolerability by Investigator | Satisfactory | 0 Participants |
| 0.1 mg | Assessment of Tolerability by Investigator | Not satisfactory | 0 Participants |
| 0.1 mg | Assessment of Tolerability by Investigator | Bad | 0 Participants |
| 0.1 mg | Assessment of Tolerability by Investigator | Not assessable | 0 Participants |
| 0.25 mg | Assessment of Tolerability by Investigator | Bad | 0 Participants |
| 0.25 mg | Assessment of Tolerability by Investigator | Not satisfactory | 0 Participants |
| 0.25 mg | Assessment of Tolerability by Investigator | Satisfactory | 0 Participants |
| 0.25 mg | Assessment of Tolerability by Investigator | Not assessable | 0 Participants |
| 0.25 mg | Assessment of Tolerability by Investigator | Good | 6 Participants |
| 0.5 mg | Assessment of Tolerability by Investigator | Bad | 0 Participants |
| 0.5 mg | Assessment of Tolerability by Investigator | Not satisfactory | 0 Participants |
| 0.5 mg | Assessment of Tolerability by Investigator | Not assessable | 0 Participants |
| 0.5 mg | Assessment of Tolerability by Investigator | Good | 1 Participants |
| 0.5 mg | Assessment of Tolerability by Investigator | Satisfactory | 0 Participants |
| 0.6 mg | Assessment of Tolerability by Investigator | Bad | 0 Participants |
| 0.6 mg | Assessment of Tolerability by Investigator | Not satisfactory | 0 Participants |
| 0.6 mg | Assessment of Tolerability by Investigator | Not assessable | 0 Participants |
| 0.6 mg | Assessment of Tolerability by Investigator | Good | 5 Participants |
| 0.6 mg | Assessment of Tolerability by Investigator | Satisfactory | 0 Participants |
Primary
Blood Pressure
Change from baseline for systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Time frame: Baseline and 28 days
Population: Treated Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Blood Pressure | SBP | 1.0 mmHg | Standard Deviation 9.4 |
| Placebo | Blood Pressure | DBP | -1.1 mmHg | Standard Deviation 3.7 |
| 0.01 mg | Blood Pressure | SBP | 1.0 mmHg | Standard Deviation 3.4 |
| 0.01 mg | Blood Pressure | DBP | -1.6 mmHg | Standard Deviation 6.8 |
| 0.03 mg | Blood Pressure | SBP | 2.8 mmHg | Standard Deviation 4.3 |
| 0.03 mg | Blood Pressure | DBP | -1.2 mmHg | Standard Deviation 2.7 |
| 0.1 mg | Blood Pressure | SBP | -3.3 mmHg | Standard Deviation 6.9 |
| 0.1 mg | Blood Pressure | DBP | -2.2 mmHg | Standard Deviation 4.2 |
| 0.25 mg | Blood Pressure | SBP | -5.8 mmHg | Standard Deviation 9.6 |
| 0.25 mg | Blood Pressure | DBP | -3.0 mmHg | Standard Deviation 3.7 |
| 0.5 mg | Blood Pressure | SBP | -16 mmHg | — |
| 0.5 mg | Blood Pressure | DBP | -12.0 mmHg | — |
| 0.6 mg | Blood Pressure | SBP | 1.4 mmHg | Standard Deviation 7 |
| 0.6 mg | Blood Pressure | DBP | 0.8 mmHg | Standard Deviation 3.6 |
Primary
Body Temperature
Change from baseline to 28 Days in Body temperature
Time frame: Baseline and 28 days
Population: Treated Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Body Temperature | 0.0 degrees celcius | Standard Deviation 0.4 |
| 0.01 mg | Body Temperature | 0.6 degrees celcius | Standard Deviation 0.4 |
| 0.03 mg | Body Temperature | -0.3 degrees celcius | Standard Deviation 0.3 |
| 0.1 mg | Body Temperature | 0.1 degrees celcius | Standard Deviation 0.5 |
| 0.25 mg | Body Temperature | -0.3 degrees celcius | Standard Deviation 0.4 |
| 0.5 mg | Body Temperature | -0.1 degrees celcius | — |
| 0.6 mg | Body Temperature | 0.2 degrees celcius | Standard Deviation 0.5 |
Primary
Number of Subjects With Drug Related Adverse Events
Number of subjects with drug related adverse events (AEs)
Time frame: From baseline up to 28 days
Population: Treated Set which included all subjects who received one dose of trial medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects With Drug Related Adverse Events | 6 Participants |
| 0.01 mg | Number of Subjects With Drug Related Adverse Events | 1 Participants |
| 0.03 mg | Number of Subjects With Drug Related Adverse Events | 5 Participants |
| 0.1 mg | Number of Subjects With Drug Related Adverse Events | 4 Participants |
| 0.25 mg | Number of Subjects With Drug Related Adverse Events | 5 Participants |
| 0.5 mg | Number of Subjects With Drug Related Adverse Events | 1 Participants |
| 0.6 mg | Number of Subjects With Drug Related Adverse Events | 1 Participants |
Primary
Pulse Rate (PR)
Change from Baseline to 28 Days in Pulse Rate
Time frame: Baseline and 28 days
Population: Treated Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pulse Rate (PR) | 0.5 bpm | Standard Deviation 12.8 |
| 0.01 mg | Pulse Rate (PR) | 6.4 bpm | Standard Deviation 6.3 |
| 0.03 mg | Pulse Rate (PR) | 6.0 bpm | Standard Deviation 5.8 |
| 0.1 mg | Pulse Rate (PR) | -0.7 bpm | Standard Deviation 6.2 |
| 0.25 mg | Pulse Rate (PR) | 0.7 bpm | Standard Deviation 5.2 |
| 0.5 mg | Pulse Rate (PR) | 3.0 bpm | — |
| 0.6 mg | Pulse Rate (PR) | 0.8 bpm | Standard Deviation 4.8 |
Primary
Respiratory Rate (RR)
Change from Baseline to 28 Days in Respiratory rate (RR)
Time frame: Baseline and 28 days
Population: Treated Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Respiratory Rate (RR) | 0.3 breaths/min | Standard Deviation 4.6 |
| 0.01 mg | Respiratory Rate (RR) | 1.2 breaths/min | Standard Deviation 5.4 |
| 0.03 mg | Respiratory Rate (RR) | 1.3 breaths/min | Standard Deviation 1.6 |
| 0.1 mg | Respiratory Rate (RR) | 0.5 breaths/min | Standard Deviation 2.1 |
| 0.25 mg | Respiratory Rate (RR) | -1.8 breaths/min | Standard Deviation 2.4 |
| 0.5 mg | Respiratory Rate (RR) | 3.0 breaths/min | — |
| 0.6 mg | Respiratory Rate (RR) | 2.0 breaths/min | Standard Deviation 3.2 |
Secondary
Amount of BI 137882 Eliminated in Urine From the Time Point t1 to Time Point t2
Amount of BI 137882 eliminated in urine from the time point t1 to time point t2 (Aet1-t2)
Time frame: 0-4, 4-8, 8-12, and 12-24 hours after drug administration
Population: There was no measurable BI 137882 excreted in urine so this pharmacokinetic parameter was not calculated.
Secondary
Apparent Clearance (CL/F)
Apparent clearance of the analyte in plasma after extravascular administration.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Clearance (CL/F) | 98.8 mL/min | Geometric Coefficient of Variation 19.6 |
| 0.01 mg | Apparent Clearance (CL/F) | 58.7 mL/min | Geometric Coefficient of Variation 27.3 |
| 0.03 mg | Apparent Clearance (CL/F) | 55.1 mL/min | Geometric Coefficient of Variation 25.2 |
Secondary
Apparent Volume of Distribution (Vz/F)
Apparent volume of distribution of the analyte during the terminal phase.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Volume of Distribution (Vz/F) | 195 L | Geometric Coefficient of Variation 11.5 |
| 0.01 mg | Apparent Volume of Distribution (Vz/F) | 182 L | Geometric Coefficient of Variation 28.2 |
| 0.03 mg | Apparent Volume of Distribution (Vz/F) | 177 L | Geometric Coefficient of Variation 9.34 |
Secondary
Area Under the Curve 0 to Infinity (AUC0-infinity)
Area under the concentration-time curve of BI 137882 in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve 0 to Infinity (AUC0-infinity) | 36.4 nmol*h/L | Geometric Coefficient of Variation 19.6 |
| 0.01 mg | Area Under the Curve 0 to Infinity (AUC0-infinity) | 153 nmol*h/L | Geometric Coefficient of Variation 27.3 |
| 0.03 mg | Area Under the Curve 0 to Infinity (AUC0-infinity) | 392 nmol*h/L | Geometric Coefficient of Variation 25.2 |
Secondary
Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 14.6 nmol*h/L | Geometric Coefficient of Variation 35.9 |
| 0.01 mg | Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 111 nmol*h/L | Geometric Coefficient of Variation 27.5 |
| 0.03 mg | Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 348 nmol*h/L | Geometric Coefficient of Variation 24.9 |
Secondary
Area Under the Effect Curve (AUEC)
Area under the effect curve for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-α/LTB4 production. A positive value indicates inhibition of the production.
Time frame: 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration
Population: Treated Set. Summary statistics were not calculated for the 0.5 mg group as there was only one patient in this group. Geometric mean and geometric coefficient of variation was not calculated for any parameter in any dose group in which zero or a negative value was calculated, as geometric means cannot be calculated with negative or zero values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Effect Curve (AUEC) | fMLP | NA pg*h/mL | — |
| Placebo | Area Under the Effect Curve (AUEC) | LPS | 25200 pg*h/mL | Geometric Coefficient of Variation 85.9 |
| 0.01 mg | Area Under the Effect Curve (AUEC) | fMLP | NA pg*h/mL | — |
| 0.01 mg | Area Under the Effect Curve (AUEC) | LPS | 34900 pg*h/mL | Geometric Coefficient of Variation 221 |
| 0.03 mg | Area Under the Effect Curve (AUEC) | LPS | 10900 pg*h/mL | Geometric Coefficient of Variation 654 |
| 0.03 mg | Area Under the Effect Curve (AUEC) | fMLP | 25700 pg*h/mL | Geometric Coefficient of Variation 6170 |
| 0.1 mg | Area Under the Effect Curve (AUEC) | LPS | NA pg*h/mL | — |
| 0.1 mg | Area Under the Effect Curve (AUEC) | fMLP | 45100 pg*h/mL | Geometric Coefficient of Variation 218 |
| 0.25 mg | Area Under the Effect Curve (AUEC) | LPS | 46900 pg*h/mL | Geometric Coefficient of Variation 492 |
| 0.25 mg | Area Under the Effect Curve (AUEC) | fMLP | NA pg*h/mL | — |
| 0.5 mg | Area Under the Effect Curve (AUEC) | fMLP | NA pg*h/mL | — |
| 0.5 mg | Area Under the Effect Curve (AUEC) | LPS | 28700 pg*h/mL | Geometric Coefficient of Variation 1050 |
Secondary
Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo.
Percent of inhibition of fMLP induction of LTB4 production. Concentrations of LTB4 in plasma were determined by an enzyme-linked immunosorbent assay (ELISA). Results indicate percent change from baseline of fMLP induction of LTB4 production. A positive value indicates inhibition of the production.
Time frame: 0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration
Population: Treated Set. Summary statistics were not calculated for the 0.5 mg group as there was only one patient in this group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 2 hours | -28.6 percentage of LTB4 production | Standard Deviation 47.3 |
| Placebo | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 6 hours | 3.57 percentage of LTB4 production | Standard Deviation 44.7 |
| Placebo | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 24 hours | -19.2 percentage of LTB4 production | Standard Deviation 58.1 |
| Placebo | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 48 hours | -48.3 percentage of LTB4 production | Standard Deviation 89.7 |
| 0.01 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 24 hours | -19.1 percentage of LTB4 production | Standard Deviation 20.2 |
| 0.01 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 6 hours | 5.26 percentage of LTB4 production | Standard Deviation 21.4 |
| 0.01 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 2 hours | -0.83 percentage of LTB4 production | Standard Deviation 16.6 |
| 0.01 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 48 hours | -38.1 percentage of LTB4 production | Standard Deviation 43.8 |
| 0.03 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 48 hours | -31.7 percentage of LTB4 production | Standard Deviation 23.2 |
| 0.03 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 24 hours | -25.3 percentage of LTB4 production | Standard Deviation 27.8 |
| 0.03 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 6 hours | 22.8 percentage of LTB4 production | Standard Deviation 29.5 |
| 0.03 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 2 hours | 15.0 percentage of LTB4 production | Standard Deviation 29.8 |
| 0.1 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 2 hours | 11.1 percentage of LTB4 production | Standard Deviation 11.3 |
| 0.1 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 48 hours | 1.11 percentage of LTB4 production | Standard Deviation 20.1 |
| 0.1 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 6 hours | 5.92 percentage of LTB4 production | Standard Deviation 15.8 |
| 0.1 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 24 hours | -12.1 percentage of LTB4 production | Standard Deviation 35 |
| 0.25 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 24 hours | -59.4 percentage of LTB4 production | Standard Deviation 66.4 |
| 0.25 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 48 hours | -41.6 percentage of LTB4 production | Standard Deviation 54.3 |
| 0.25 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 6 hours | -8.73 percentage of LTB4 production | Standard Deviation 39.3 |
| 0.25 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 2 hours | -29.6 percentage of LTB4 production | Standard Deviation 35.6 |
| 0.5 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 6 hours | -69.1 percentage of LTB4 production | Standard Deviation 74 |
| 0.5 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 24 hours | -61.2 percentage of LTB4 production | Standard Deviation 49.7 |
| 0.5 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 48 hours | -94.2 percentage of LTB4 production | Standard Deviation 44.9 |
| 0.5 mg | Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo. | 2 hours | -74.4 percentage of LTB4 production | Standard Deviation 48.2 |
Secondary
Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo
Concentrations of TNF-α in plasma were determined by an enzyme-linked immunosorbent assay (ELISA). Concentrations of TNF-α in blood drawn after treatment with BI 137882 were compared with those in pre-dose samples to calculate the percent of inhibition of LPS induction of TNF-α production. Results indicate percent change from baseline of LPS-induced TNF-α production. A positive value indicates inhibition of the production.
Time frame: 0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration
Population: Treated Set. Summary statistics were not calculated for the 0.5 mg group as there was only one patient in this group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 2 hours | -26.3 percentage of TNF-α production | Standard Deviation 45 |
| Placebo | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 6 hours | 1.13 percentage of TNF-α production | Standard Deviation 64.5 |
| Placebo | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 24 hours | -23.2 percentage of TNF-α production | Standard Deviation 41.8 |
| Placebo | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 48 hours | -13.8 percentage of TNF-α production | Standard Deviation 44.3 |
| 0.01 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 24 hours | -11.6 percentage of TNF-α production | Standard Deviation 30.3 |
| 0.01 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 2 hours | -23.1 percentage of TNF-α production | Standard Deviation 35.6 |
| 0.01 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 6 hours | 37.9 percentage of TNF-α production | Standard Deviation 19.5 |
| 0.01 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 48 hours | -3.90 percentage of TNF-α production | Standard Deviation 56.9 |
| 0.03 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 6 hours | -5.29 percentage of TNF-α production | Standard Deviation 34.7 |
| 0.03 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 24 hours | 2.05 percentage of TNF-α production | Standard Deviation 20.7 |
| 0.03 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 2 hours | -59.1 percentage of TNF-α production | Standard Deviation 35.9 |
| 0.03 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 48 hours | 7.49 percentage of TNF-α production | Standard Deviation 33 |
| 0.1 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 2 hours | -23.9 percentage of TNF-α production | Standard Deviation 24 |
| 0.1 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 6 hours | 11.4 percentage of TNF-α production | Standard Deviation 25.3 |
| 0.1 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 24 hours | -16.4 percentage of TNF-α production | Standard Deviation 41.7 |
| 0.1 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 48 hours | -61.0 percentage of TNF-α production | Standard Deviation 122 |
| 0.25 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 24 hours | 4.78 percentage of TNF-α production | Standard Deviation 36.5 |
| 0.25 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 6 hours | -2.17 percentage of TNF-α production | Standard Deviation 60.5 |
| 0.25 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 2 hours | 1.13 percentage of TNF-α production | Standard Deviation 20 |
| 0.25 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 48 hours | -0.98 percentage of TNF-α production | Standard Deviation 22.6 |
| 0.5 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 2 hours | -0.41 percentage of TNF-α production | Standard Deviation 28.3 |
| 0.5 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 48 hours | 3.52 percentage of TNF-α production | Standard Deviation 51.5 |
| 0.5 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 6 hours | 12.8 percentage of TNF-α production | Standard Deviation 54.2 |
| 0.5 mg | Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo | 24 hours | -17.1 percentage of TNF-α production | Standard Deviation 64.6 |
Secondary
Fraction of BI 137882 Eliminated in Urine From Time Point t1 to Time Point t2
Fraction of BI 137882 eliminated in urine from time point t1 to time point t2 (fet1-t2)
Time frame: 0-4, 4-8, 8-12, and 12-24 hours after drug administration
Population: There was no measurable BI 137882 excreted in urine so this pharmacokinetic parameter was not calculated.
Secondary
Maximum Effect (Emax)
Maximum effect for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-α/LTB4 production. A positive value indicates inhibition of the production.
Time frame: 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration
Population: Treated Set. Summary statistics were not calculated for the 0.5 mg group as there was only one patient in this group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Effect (Emax) | TNF-alpha induced by LPS | 13400 pg/mL | Geometric Coefficient of Variation 42.9 |
| Placebo | Maximum Effect (Emax) | LTB4 induced by fMLP | 60400 pg/mL | Geometric Coefficient of Variation 81.2 |
| 0.01 mg | Maximum Effect (Emax) | TNF-alpha induced by LPS | 12000 pg/mL | Geometric Coefficient of Variation 30.1 |
| 0.01 mg | Maximum Effect (Emax) | LTB4 induced by fMLP | 49400 pg/mL | Geometric Coefficient of Variation 28.5 |
| 0.03 mg | Maximum Effect (Emax) | TNF-alpha induced by LPS | 9990 pg/mL | Geometric Coefficient of Variation 43.3 |
| 0.03 mg | Maximum Effect (Emax) | LTB4 induced by fMLP | 51300 pg/mL | Geometric Coefficient of Variation 17.3 |
| 0.1 mg | Maximum Effect (Emax) | TNF-alpha induced by LPS | 18200 pg/mL | Geometric Coefficient of Variation 47.3 |
| 0.1 mg | Maximum Effect (Emax) | LTB4 induced by fMLP | 27800 pg/mL | Geometric Coefficient of Variation 64.4 |
| 0.25 mg | Maximum Effect (Emax) | TNF-alpha induced by LPS | 21500 pg/mL | Geometric Coefficient of Variation 39.5 |
| 0.25 mg | Maximum Effect (Emax) | LTB4 induced by fMLP | 44800 pg/mL | Geometric Coefficient of Variation 37.1 |
| 0.5 mg | Maximum Effect (Emax) | TNF-alpha induced by LPS | 13800 pg/mL | Geometric Coefficient of Variation 32.9 |
| 0.5 mg | Maximum Effect (Emax) | LTB4 induced by fMLP | 42100 pg/mL | Geometric Coefficient of Variation 46.3 |
Secondary
Maximum Measured Concentration (Cmax)
Maximum measured concentration of BI 137882 in plasma.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration (Cmax) | 1.37 nmol/L | Geometric Coefficient of Variation 20 |
| 0.01 mg | Maximum Measured Concentration (Cmax) | 4.79 nmol/L | Geometric Coefficient of Variation 25.6 |
| 0.03 mg | Maximum Measured Concentration (Cmax) | 11.2 nmol/L | Geometric Coefficient of Variation 21.7 |
Secondary
Mean Residence Time (MRTpo)
Mean residence time of the analyte in the body after oral administration.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Residence Time (MRTpo) | 32.9 hours | Geometric Coefficient of Variation 16.5 |
| 0.01 mg | Mean Residence Time (MRTpo) | 49.6 hours | Geometric Coefficient of Variation 41.1 |
| 0.03 mg | Mean Residence Time (MRTpo) | 52.8 hours | Geometric Coefficient of Variation 26 |
Secondary
Minimum Effect (Emin)
Minimum effect for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-α/LTB4 production. A positive value indicates inhibition of the production.
Time frame: 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration
Population: Treated Set. Summary statistics were not calculated for the 0.5 mg group as there was only one patient in this group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Minimum Effect (Emin) | TNF-alpha induced by LPS | 5200 pg/mL | Geometric Coefficient of Variation 50.7 |
| Placebo | Minimum Effect (Emin) | LTB4 induced by fMLP | 29000 pg/mL | Geometric Coefficient of Variation 67.8 |
| 0.01 mg | Minimum Effect (Emin) | TNF-alpha induced by LPS | 5500 pg/mL | Geometric Coefficient of Variation 25.5 |
| 0.01 mg | Minimum Effect (Emin) | LTB4 induced by fMLP | 31100 pg/mL | Geometric Coefficient of Variation 42.9 |
| 0.03 mg | Minimum Effect (Emin) | TNF-alpha induced by LPS | 4730 pg/mL | Geometric Coefficient of Variation 57.7 |
| 0.03 mg | Minimum Effect (Emin) | LTB4 induced by fMLP | 24000 pg/mL | Geometric Coefficient of Variation 32.4 |
| 0.1 mg | Minimum Effect (Emin) | TNF-alpha induced by LPS | 8210 pg/mL | Geometric Coefficient of Variation 43.5 |
| 0.1 mg | Minimum Effect (Emin) | LTB4 induced by fMLP | 19000 pg/mL | Geometric Coefficient of Variation 52.7 |
| 0.25 mg | Minimum Effect (Emin) | TNF-alpha induced by LPS | 9570 pg/mL | Geometric Coefficient of Variation 63.5 |
| 0.25 mg | Minimum Effect (Emin) | LTB4 induced by fMLP | 19500 pg/mL | Geometric Coefficient of Variation 31.4 |
| 0.5 mg | Minimum Effect (Emin) | TNF-alpha induced by LPS | 5890 pg/mL | Geometric Coefficient of Variation 63.6 |
| 0.5 mg | Minimum Effect (Emin) | LTB4 induced by fMLP | 19900 pg/mL | Geometric Coefficient of Variation 56.5 |
Secondary
Renal Clearance of BI 137882 From the Time Point t1 Until the Time Point t2
Renal clearance of BI 137882 from the time point t1 until the time point t2 (CLR,t1-t2)
Time frame: 0-4, 4-8, 8-12, and 12-24 hours after drug administration
Population: There was no measurable BI 137882 excreted in urine so this pharmacokinetic parameter was not calculated.
Secondary
Terminal Half-life (t1/2)
Terminal half-life of BI 137882 in plasma.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Half-life (t1/2) | 22.8 hours | Geometric Coefficient of Variation 17.7 |
| 0.01 mg | Terminal Half-life (t1/2) | 35.8 hours | Geometric Coefficient of Variation 46.8 |
| 0.03 mg | Terminal Half-life (t1/2) | 37.2 hours | Geometric Coefficient of Variation 27 |
Secondary
Terminal Rate Constant (λz)
Terminal rate constant in plasma.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Rate Constant (λz) | 0.0304 1/h | Geometric Coefficient of Variation 17.7 |
| 0.01 mg | Terminal Rate Constant (λz) | 0.0194 1/h | Geometric Coefficient of Variation 46.8 |
| 0.03 mg | Terminal Rate Constant (λz) | 0.0186 1/h | Geometric Coefficient of Variation 27 |
Secondary
Time to Maximum Measured Concentration (Tmax)
Time from dosing to maximum measured concentration of the analyte in plasma.
Time frame: 30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration
Population: Treated Set. Descriptive statistics are only presented for treatment groups where the summary statistics were calculated.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Maximum Measured Concentration (Tmax) | 1.99 hours | Full Range 68.8 |
| 0.01 mg | Time to Maximum Measured Concentration (Tmax) | 1.48 hours | Full Range 62.9 |
| 0.03 mg | Time to Maximum Measured Concentration (Tmax) | 0.99 hours | Full Range 115 |