Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the safety and tolerability of BI 655130 in healthy male subjects following IV administration of multiple rising doses. The study will also explore safety and tolerability following a single IV administration.
Interventions
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (BP - Blood Pressure, PR - Pulse Rate), 12-lead ECG (Electrocardiogram), and clinical laboratory tests * Age of 18 to 50 years (incl.) * BMI of 18.5 to 29.9 kg/m2 (incl.) * Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
Exclusion criteria
* Any finding in the medical examination (including BP - Blood Pressure, PR - Pulse Rate or ECG - Electrocardiogram) is deviating from normal and judged 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 judged as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug-related Adverse Events (AEs). | From first drug administration until the end-of-trial examination; up to 179 days. (For both, Multiple rising dose part and single dose part) | Percentage of subjects with investigator defined drug-related adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Pharmacokinetic samples were collected at 2 hours pre-dose and 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration. | AUC0-∞, Area under the concentration-time curve of the BI 655130 in plasma over the time interval from 0 extrapolated to infinity. This endpoint only applies to the single rising dose part (SD) (20 mg/kg BI 655130 single dose). |
| Maximum Measured Concentration of the BI 655130 in Plasma (Cmax) | Up to 4200 hours. Individual time points are provided in detail in description. | Cmax, maximum measured concentration of BI 655130 in plasma for single dose and multiple dose. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg SD: Samples were collected at 2 h pre-dose, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 h after dosing. |
| Maximum Measured Concentration of BI 655130 in Plasma After the Fourth Dose (Cmax,4) | Up to 4200 hours. Individual time points are provided in detail in description. | Cmax,4, maximum measured concentration of BI 655130 in plasma after the fourth dose. Steady state was not reached, therefore Cmax,ss is presented as Cmax,4. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. |
| Area Under the Concentration-time Curve of the BI 655130 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1) | Up to 4200 hours. Individual time points are provided in detail in description. | AUCτ,1, Area under the concentration-time curve of the BI 655130 in plasma over a uniform dosing interval τ after administration of the first dose. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. |
| Area Under the Concentration Time Curve of BI 655130 in Plasma After the Fourth Dose (AUCτ,4) | Up to 4200 hours. Individual time points are provided in detail in description. | AUCτ,4, area under the concentration time curve of BI 655130 in plasma after the fourth dose. Steady state was not reached, therefore AUCτ,ss is presented as AUCτ,4. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. |
Countries
Belgium
Participant flow
Recruitment details
The multiple rising dose (MRD) part of the trial was double-blind, randomised and placebo-controlled within parallel dose groups. The placebo-controlled single dose (SD) part was single-blind and partially randomised.
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites to ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be randomized to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching to BI 655130 Multiple Dose (MD) Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130. | 8 |
| 3 Milligram/Kilogram (mg/kg)] BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130 | 6 |
| 6 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130. | 6 |
| 10 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130. | 6 |
| 20 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130. | 6 |
| Placebo Matching to BI 655130 Single Dose (SD) Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130. | 2 |
| 20 mg/kg BI 655130 Single Dose Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130. | 6 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo Matching to BI 655130 Multiple Dose (MD) | 3 Milligram/Kilogram (mg/kg)] BI 655130 MD | 6 mg/kg BI 655130 MD | 10 mg/kg BI 655130 MD | 20 mg/kg BI 655130 MD | Placebo Matching to BI 655130 Single Dose (SD) | 20 mg/kg BI 655130 Single Dose | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.9 Years STANDARD_DEVIATION 7.3 | 37.7 Years STANDARD_DEVIATION 8.9 | 35.3 Years STANDARD_DEVIATION 6.4 | 31.0 Years STANDARD_DEVIATION 9.1 | 37.2 Years STANDARD_DEVIATION 7.4 | 46.5 Years STANDARD_DEVIATION 4.9 | 37.5 Years STANDARD_DEVIATION 9.9 | 36.3 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 2 Participants | 6 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 40 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 | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 40 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 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 |
| other Total, other adverse events | 8 / 8 | 5 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 2 / 2 | 4 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 |
Outcome results
Primary
Percentage of Subjects With Drug-related Adverse Events (AEs).
Percentage of subjects with investigator defined drug-related adverse events (AEs).
Time frame: From first drug administration until the end-of-trial examination; up to 179 days. (For both, Multiple rising dose part and single dose part)
Population: Treated set (TS): This subject set included all subjects who received trial drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching to BI 655130 Multiple Dose (MD) | Percentage of Subjects With Drug-related Adverse Events (AEs). | 50.0 Percentage of participants |
| 3 Milligram/Kilogram (mg/kg)] BI 655130 MD | Percentage of Subjects With Drug-related Adverse Events (AEs). | 16.7 Percentage of participants |
| 6 mg/kg BI 655130 MD | Percentage of Subjects With Drug-related Adverse Events (AEs). | 66.7 Percentage of participants |
| 10 mg/kg BI 655130 MD | Percentage of Subjects With Drug-related Adverse Events (AEs). | 33.3 Percentage of participants |
| 20 mg/kg BI 655130 MD | Percentage of Subjects With Drug-related Adverse Events (AEs). | 100.0 Percentage of participants |
| Placebo Matching to BI 655130 Single Dose (SD) | Percentage of Subjects With Drug-related Adverse Events (AEs). | 0.0 Percentage of participants |
| 20 mg/kg BI 655130 Single Dose | Percentage of Subjects With Drug-related Adverse Events (AEs). | 33.3 Percentage of participants |
Secondary
Area Under the Concentration Time Curve of BI 655130 in Plasma After the Fourth Dose (AUCτ,4)
AUCτ,4, area under the concentration time curve of BI 655130 in plasma after the fourth dose. Steady state was not reached, therefore AUCτ,ss is presented as AUCτ,4. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing.
Time frame: Up to 4200 hours. Individual time points are provided in detail in description.
Population: Pharmacokinetic parameter set (PKS):This subject set included all subjects of the TS who provided at least 1 observation for at least 1 secondary PK endpoint without important protocol violations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI 655130 Multiple Dose (MD) | Area Under the Concentration Time Curve of BI 655130 in Plasma After the Fourth Dose (AUCτ,4) | 760.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 4.21 |
| 3 Milligram/Kilogram (mg/kg)] BI 655130 MD | Area Under the Concentration Time Curve of BI 655130 in Plasma After the Fourth Dose (AUCτ,4) | 1390.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 4.63 |
| 6 mg/kg BI 655130 MD | Area Under the Concentration Time Curve of BI 655130 in Plasma After the Fourth Dose (AUCτ,4) | 2500.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 16.7 |
| 10 mg/kg BI 655130 MD | Area Under the Concentration Time Curve of BI 655130 in Plasma After the Fourth Dose (AUCτ,4) | 4660.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 12.9 |
Comparison: Dose proportionality was explored using a regression model. A 95% confidence interval (CI) for the slope was computed. Power model is used as statistical method.95% CI: [0.8975, 1.044]
Secondary
Area Under the Concentration-time Curve of the BI 655130 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1)
AUCτ,1, Area under the concentration-time curve of the BI 655130 in plasma over a uniform dosing interval τ after administration of the first dose. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing.
Time frame: Up to 4200 hours. Individual time points are provided in detail in description.
Population: Pharmacokinetic parameter set (PKS):This subject set included all subjects of the TS who provided at least 1 observation for at least 1 secondary PK endpoint without important protocol violations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI 655130 Multiple Dose (MD) | Area Under the Concentration-time Curve of the BI 655130 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1) | 298.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 9.26 |
| 3 Milligram/Kilogram (mg/kg)] BI 655130 MD | Area Under the Concentration-time Curve of the BI 655130 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1) | 552.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 10.4 |
| 6 mg/kg BI 655130 MD | Area Under the Concentration-time Curve of the BI 655130 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1) | 923.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 17.3 |
| 10 mg/kg BI 655130 MD | Area Under the Concentration-time Curve of the BI 655130 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1) | 1770.00 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 12.5 |
Comparison: Dose proportionality was explored using a regression model. A 95% confidence interval (CI) for the slope was computed. Power model is used as statistical method.95% CI: [0.8697, 1.0182]
Secondary
Area Under the Concentration-time Curve of the BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞, Area under the concentration-time curve of the BI 655130 in plasma over the time interval from 0 extrapolated to infinity. This endpoint only applies to the single rising dose part (SD) (20 mg/kg BI 655130 single dose).
Time frame: Pharmacokinetic samples were collected at 2 hours pre-dose and 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration.
Population: Pharmacokinetic parameter set (PKS):This subject set included all subjects of the TS who provided at least 1 observation for at least 1 secondary PK endpoint without important protocol violations with respect to the statistical evaluation of PK endpoints. Only subjects from SRD part were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI 655130 Multiple Dose (MD) | Area Under the Concentration-time Curve of the BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 10500 microgram*day/milliliter [μg*day/mL] | Geometric Coefficient of Variation 19.2 |
Secondary
Maximum Measured Concentration of BI 655130 in Plasma After the Fourth Dose (Cmax,4)
Cmax,4, maximum measured concentration of BI 655130 in plasma after the fourth dose. Steady state was not reached, therefore Cmax,ss is presented as Cmax,4. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing.
Time frame: Up to 4200 hours. Individual time points are provided in detail in description.
Population: Pharmacokinetic parameter set (PKS):This subject set included all subjects of the TS who provided at least 1 observation for at least 1 secondary PK endpoint without important protocol violations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI 655130 Multiple Dose (MD) | Maximum Measured Concentration of BI 655130 in Plasma After the Fourth Dose (Cmax,4) | 141.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 4.33 |
| 3 Milligram/Kilogram (mg/kg)] BI 655130 MD | Maximum Measured Concentration of BI 655130 in Plasma After the Fourth Dose (Cmax,4) | 253.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 8.7 |
| 6 mg/kg BI 655130 MD | Maximum Measured Concentration of BI 655130 in Plasma After the Fourth Dose (Cmax,4) | 467.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 21.4 |
| 10 mg/kg BI 655130 MD | Maximum Measured Concentration of BI 655130 in Plasma After the Fourth Dose (Cmax,4) | 826.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 15.8 |
Comparison: Dose proportionality was explored using a regression model. A 95% confidence interval (CI) for the slope was computed. Power model is used as statistical method.95% CI: [0.8581, 1.0475]
Secondary
Maximum Measured Concentration of the BI 655130 in Plasma (Cmax)
Cmax, maximum measured concentration of BI 655130 in plasma for single dose and multiple dose. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg SD: Samples were collected at 2 h pre-dose, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 h after dosing.
Time frame: Up to 4200 hours. Individual time points are provided in detail in description.
Population: Pharmacokinetic parameter set (PKS):This subject set included all subjects of the TS who provided at least 1 observation for at least 1 secondary PK endpoint without important protocol violations with respect to the statistical evaluation of PK endpoints. Subjects in SRD and MRD part were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI 655130 Multiple Dose (MD) | Maximum Measured Concentration of the BI 655130 in Plasma (Cmax) | 77.90 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 19.4 |
| 3 Milligram/Kilogram (mg/kg)] BI 655130 MD | Maximum Measured Concentration of the BI 655130 in Plasma (Cmax) | 130.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 8.48 |
| 6 mg/kg BI 655130 MD | Maximum Measured Concentration of the BI 655130 in Plasma (Cmax) | 229.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 22.9 |
| 10 mg/kg BI 655130 MD | Maximum Measured Concentration of the BI 655130 in Plasma (Cmax) | 422.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 18.5 |
| 20 mg/kg BI 655130 MD | Maximum Measured Concentration of the BI 655130 in Plasma (Cmax) | 490.00 microgram/milliliter [μg/mL] | Geometric Coefficient of Variation 29 |
Comparison: Dose proportionality was explored using a regression model. A 95% confidence interval (CI) for the slope was computed. Power model is used a statistical method.95% CI: [0.7973, 1.0142]