Healthy
Conditions
Brief summary
Investigation of safety and tolerability of BI 655088 following intravenous infusion of single rising doses and exploration of the pharmacokinetics and pharmacodynamics of BI 655088 after single dosing
Interventions
DRUGBI 655088
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects * Age of 18 to 50 years * Body mass index (BMI) of 18.5 to 29.9 kg/m2 * Additional inclusion criteria may apply
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) 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 or 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 and stroke), and other relevant neurological disorders or psychiatric disorders * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Drug-related Adverse Events | up to 99 days after start of drug administration | The number of subjects with drug-related adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 655088 in Plasma (Cmax) | Up to 2016 hours. See endpoint description for a detailed timeframe. | Maximum measured concentration of BI 655088 in plasma (Cmax). Time frame for all dose groups: within 3 hours before and 10, 24, 36, 48, 72, 96, 120, 144, 168, 264, 336, 432, 504, 600, 672, 840, 1008, 1176, 1344, 1512, 1680 and 2016 hours following start of infusion. In additional, the following time points for the 2 milligram group: 0.25, 0.5, 1, 1.5, 2.25, 2.5, 3, 6, 8, 12 and 30 hours following start of infusion. |
| Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Up to 2016 hours. See endpoint description for a detailed timeframe. | AUC0-tz (area under the concentration-time curve of BI 655088 in plasma over the time interval from 0 to the last quantifiable data point). Time frame for all dose groups: within 3 hours before and 10, 24, 36, 48, 72, 96, 120, 144, 168, 264, 336, 432, 504, 600, 672, 840, 1008, 1176, 1344, 1512, 1680 and 2016 hours following start of infusion. In additional, the following time points for the 2 milligram group: 0.25, 0.5, 1, 1.5, 2.25, 2.5, 3, 6, 8, 12 and 30 hours following start of infusion. |
| Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Up to 2016 hours. See endpoint description for a detailed timeframe. | AUC0-∞ (area under the concentration-time curve of BI 655088 in plasma over the time interval from 0 extrapolated to infinity). Time frame for all dose groups: within 3 hours before and 10, 24, 36, 48, 72, 96, 120, 144, 168, 264, 336, 432, 504, 600, 672, 840, 1008, 1176, 1344, 1512, 1680 and 2016 hours following start of infusion. In additional, the following time points for the 2 milligram group: 0.25, 0.5, 1, 1.5, 2.25, 2.5, 3, 6, 8, 12 and 30 hours following start of infusion. |
Countries
Belgium
Participant flow
Recruitment details
Single-rising dose trial, partially randomised within dose groups, placebo-controlled, single-blind, parallel-group design with 6 dose groups.
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that the subjects met all strictly implemented inclusion and none of the exclusion criteria. Subjects would not have been treated with the trial treatment if any one of the specific entry criteria had been violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Comparator product: Matching Placebo to BI 655088 (buffer solution).
Mode of administration: Intravenous (IV) infusion for 120 minutes | 12 |
| BI 655088 2 mg BI investigational product: Single Dose of 2 milligram (mg) of BI 655088 as solution for infusion (10 mg/millilitre (mL) in buffer solution).
Mode of administration: IV infusion for 120 minutes | 5 |
| BI 655088 6 mg BI investigational product: Single Dose of 6mg of BI 655088 as solution for infusion (10 mg/mL in buffer solution).
Mode of administration: IV infusion for 120 minutes | 6 |
| BI 655088 20 mg BI investigational product: Single Dose of 20mg of BI 655088 as solution for infusion (10 mg/mL in buffer solution).
Mode of administration: IV infusion for 120 minutes | 6 |
| BI 655088 50 mg BI investigational product: Single Dose of 50mg of BI 655088 as solution for infusion (10 mg/mL in buffer solution).
Mode of administration: IV infusion for 120 minutes | 6 |
| BI 655088 100 mg BI investigational product: Single Dose of 100mg of BI 655088 as solution for infusion (10 mg/mL in buffer solution).
Mode of administration: IV infusion for 120 minutes | 6 |
| BI 655088 200 mg BI investigational product: Single Dose of 200mg of BI 655088 as solution for infusion (10 mg/mL in buffer solution).
Mode of administration: IV infusion for 120 minutes | 6 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | BI 655088 20 mg | Placebo | BI 655088 2 mg | BI 655088 6 mg | BI 655088 50 mg | BI 655088 100 mg | BI 655088 200 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 7.5 | 36.3 years STANDARD_DEVIATION 8.5 | 42.0 years STANDARD_DEVIATION 9.4 | 33.0 years STANDARD_DEVIATION 5 | 43.7 years STANDARD_DEVIATION 6.3 | 34.0 years STANDARD_DEVIATION 9.7 | 37.8 years STANDARD_DEVIATION 9.5 | 38.1 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 11 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 46 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 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 6 Participants | 10 Participants | 4 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 42 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 | 6 Participants | 12 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 47 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 / 12 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 10 / 12 | 4 / 5 | 3 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 12 | 1 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 |
Outcome results
Primary
Number of Subjects With Drug-related Adverse Events
The number of subjects with drug-related adverse events.
Time frame: up to 99 days after start of drug administration
Population: Treated set:~This subject set included all subjects who were documented to have received at least~1 dose of trial drug. It was used for analysis of safety, demographic data, and baseline characteristics, and disposition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects With Drug-related Adverse Events | 2 Participants |
| BI 655088 2 mg | Number of Subjects With Drug-related Adverse Events | 1 Participants |
| BI 655088 6 mg | Number of Subjects With Drug-related Adverse Events | 2 Participants |
| BI 655088 20 mg | Number of Subjects With Drug-related Adverse Events | 1 Participants |
| BI 655088 50 mg | Number of Subjects With Drug-related Adverse Events | 0 Participants |
| BI 655088 100 mg | Number of Subjects With Drug-related Adverse Events | 0 Participants |
| BI 655088 200 mg | Number of Subjects With Drug-related Adverse Events | 0 Participants |
Secondary
Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
AUC0-∞ (area under the concentration-time curve of BI 655088 in plasma over the time interval from 0 extrapolated to infinity). Time frame for all dose groups: within 3 hours before and 10, 24, 36, 48, 72, 96, 120, 144, 168, 264, 336, 432, 504, 600, 672, 840, 1008, 1176, 1344, 1512, 1680 and 2016 hours following start of infusion. In additional, the following time points for the 2 milligram group: 0.25, 0.5, 1, 1.5, 2.25, 2.5, 3, 6, 8, 12 and 30 hours following start of infusion.
Time frame: Up to 2016 hours. See endpoint description for a detailed timeframe.
Population: Pharmacokinetic (PK) parameter analysis set:~This subject set included all subjects who were documented to have received at least~1 dose of BI 655088 and who provided at least 1 PK endpoint value that was not excluded (due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 12.9 microgram (µg)∙hour (h) /millilitre(mL) | Geometric Coefficient of Variation 24.4 |
| BI 655088 2 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 65.7 microgram (µg)∙hour (h) /millilitre(mL) | Geometric Coefficient of Variation 11.9 |
| BI 655088 6 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 395 microgram (µg)∙hour (h) /millilitre(mL) | Geometric Coefficient of Variation 21.3 |
| BI 655088 20 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 1250 microgram (µg)∙hour (h) /millilitre(mL) | Geometric Coefficient of Variation 17 |
| BI 655088 50 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 2360 microgram (µg)∙hour (h) /millilitre(mL) | Geometric Coefficient of Variation 124 |
| BI 655088 100 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 7010 microgram (µg)∙hour (h) /millilitre(mL) | Geometric Coefficient of Variation 17.9 |
Secondary
Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
AUC0-tz (area under the concentration-time curve of BI 655088 in plasma over the time interval from 0 to the last quantifiable data point). Time frame for all dose groups: within 3 hours before and 10, 24, 36, 48, 72, 96, 120, 144, 168, 264, 336, 432, 504, 600, 672, 840, 1008, 1176, 1344, 1512, 1680 and 2016 hours following start of infusion. In additional, the following time points for the 2 milligram group: 0.25, 0.5, 1, 1.5, 2.25, 2.5, 3, 6, 8, 12 and 30 hours following start of infusion.
Time frame: Up to 2016 hours. See endpoint description for a detailed timeframe.
Population: Pharmacokinetic (PK) parameter analysis set: This subject set included all subjects who were documented to have received at least 1 dose of BI 655088 and who provided at least 1 PK endpoint value that was not excluded (due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability). 1 subject was excluded from the 200 mg group due to missing samples after 840 hours.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 12.5 microgram (µg)∙hour (h)/millilitre (mL) | Geometric Coefficient of Variation 22.8 |
| BI 655088 2 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 63.8 microgram (µg)∙hour (h)/millilitre (mL) | Geometric Coefficient of Variation 13.2 |
| BI 655088 6 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 392 microgram (µg)∙hour (h)/millilitre (mL) | Geometric Coefficient of Variation 21.2 |
| BI 655088 20 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 1250 microgram (µg)∙hour (h)/millilitre (mL) | Geometric Coefficient of Variation 17 |
| BI 655088 50 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2360 microgram (µg)∙hour (h)/millilitre (mL) | Geometric Coefficient of Variation 124 |
| BI 655088 100 mg | Area Under the Concentration-time Curve of BI 655088 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 7210 microgram (µg)∙hour (h)/millilitre (mL) | Geometric Coefficient of Variation 18.3 |
Secondary
Maximum Measured Concentration of BI 655088 in Plasma (Cmax)
Maximum measured concentration of BI 655088 in plasma (Cmax). Time frame for all dose groups: within 3 hours before and 10, 24, 36, 48, 72, 96, 120, 144, 168, 264, 336, 432, 504, 600, 672, 840, 1008, 1176, 1344, 1512, 1680 and 2016 hours following start of infusion. In additional, the following time points for the 2 milligram group: 0.25, 0.5, 1, 1.5, 2.25, 2.5, 3, 6, 8, 12 and 30 hours following start of infusion.
Time frame: Up to 2016 hours. See endpoint description for a detailed timeframe.
Population: Pharmacokinetic (PK) parameter analysis set:~This subject set included all subjects who were documented to have received at least~1 dose of BI 655088 and who provided at least 1 PK endpoint value that was not excluded (due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 655088 in Plasma (Cmax) | 0.593 microgram (µg) / millilitre (mL) | Geometric Coefficient of Variation 8.98 |
| BI 655088 2 mg | Maximum Measured Concentration of BI 655088 in Plasma (Cmax) | 1.69 microgram (µg) / millilitre (mL) | Geometric Coefficient of Variation 15.8 |
| BI 655088 6 mg | Maximum Measured Concentration of BI 655088 in Plasma (Cmax) | 5.76 microgram (µg) / millilitre (mL) | Geometric Coefficient of Variation 24.9 |
| BI 655088 20 mg | Maximum Measured Concentration of BI 655088 in Plasma (Cmax) | 13.1 microgram (µg) / millilitre (mL) | Geometric Coefficient of Variation 12.5 |
| BI 655088 50 mg | Maximum Measured Concentration of BI 655088 in Plasma (Cmax) | 17.3 microgram (µg) / millilitre (mL) | Geometric Coefficient of Variation 66.2 |
| BI 655088 100 mg | Maximum Measured Concentration of BI 655088 in Plasma (Cmax) | 48.8 microgram (µg) / millilitre (mL) | Geometric Coefficient of Variation 4.9 |