Healthy
Conditions
Brief summary
Safety, tolerability, pharmacokinetics and pharmacodynamics of BI 655064 after single rising doses in healthy Asian male volunteers.
Interventions
DRUGPlacebo
Solution for subcutaneous (s.c.) injection.
DRUGBI 655064
Solution for subcutaneous (s.c.) injection.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests * Chinese ethnicity, Japanese ethnicity according to the following criteria. Japanese: born in Japan, have lived outside of Japan \<10 years, and have parents and grandparents who were all born in Japan. Chinese: ethnic Chinese, born in China or ethnic Chinese born outside of China, and a descendent of 4 ethnic Chinese grandparents who were all born in China * Age within the range of 20 to 45 years inclusive * Body mass index within the range of 18.5 and 25 kg/m2 inclusive * Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
Exclusion criteria
* Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance * Any disease or clinically relevant abnormality in laboratory parameters which, according to the investigator, might compromise the safety of the subject or interfere with the subjects participation in the trial or compromise the trial objectives * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders * History of relevant orthostatic hypotension, fainting spells or blackouts. * Chronic or relevant acute infections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Investigator Defined Drug-related Adverse Events | From study drug administration until end-of-study examination, up to 77 days. | Number of participants with investigator defined drug-related adverse events (AEs) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Within 3:00 hours:minutes (h:min) before and 08:00h, 12:00h, 24:00h, 36:00h, 48:00h, 72:00h, 96:00h, 108:00h, 120:00h, 168:00h, 264:00h, 432:00h, 648:00h, 984:00h, 1320:00h, 1656:00 h:min after BI 655064 administration. | Maximum measured concentration of BI 655064 in plasma (Cmax) is reported. |
| Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3:00 hours:minutes (h:min) before and 08:00h, 12:00h, 24:00h, 36:00h, 48:00h, 72:00h, 96:00h, 108:00h, 120:00h, 168:00h, 264:00h, 432:00h, 648:00h, 984:00h, 1320:00h, 1656:00 h:min after BI 655064 administration. | Area under the concentration-time curve of the analyte BI 655064 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. |
| Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Within 3:00 hours:minutes (h:min) before and 08:00h, 12:00h, 24:00h, 36:00h, 48:00h, 72:00h, 96:00h, 108:00h, 120:00h, 168:00h, 264:00h, 432:00h, 648:00h, 984:00h, 1320:00h, 1656:00 h:min after BI 655064 administration. | Area under the concentration-time curve of the analyte BI 655064 in the plasma over the time interval from 0 to the last measurable time point (AUC0-tz) is reported. |
Countries
Japan, South Korea
Participant flow
Recruitment details
This was a randomised, placebo-controlled, double-blind within dose groups, single rising dose study with 4 doses in Chinese and Japanese healthy volunteers.
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 |
|---|---|
| BI 655064 Dose Group 1 - 80 mg Japanese and Chinese healthy participants were administered subcutaneously (s.c.) a single dose of 80 milligram (mg) of solution for injection of BI 655064. | 12 |
| BI 655064 Dose Group 2 - 120 mg Japanese and Chinese healthy participants were administered subcutaneously (s.c.) a single dose of 120 milligram (mg) of solution for injection of BI 655064. | 12 |
| BI 655064 Dose Group 3 - 180 mg Japanese and Chinese healthy participants were administered subcutaneously (s.c.) a single dose of 180 milligram (mg) of solution for injection of BI 655064. | 12 |
| BI 655064 Dose Group 4 - 240 mg Japanese and Chinese healthy participants were administered subcutaneously (s.c.) a single dose of 240 milligram (mg) of solution for injection of BI 655064. | 12 |
| Placebo Matching BI 655064 Japanese and Chinese healthy participants were administered subcutaneously (s.c.) a single dose of solution for injection of Placebo matching BI 655064. | 16 |
| Total | 64 |
Baseline characteristics
| Characteristic | BI 655064 Dose Group 1 - 80 mg | BI 655064 Dose Group 2 - 120 mg | BI 655064 Dose Group 3 - 180 mg | BI 655064 Dose Group 4 - 240 mg | Placebo Matching BI 655064 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 27.5 Years STANDARD_DEVIATION 6.7 | 24.6 Years STANDARD_DEVIATION 2.6 | 26.7 Years STANDARD_DEVIATION 6 | 29.7 Years STANDARD_DEVIATION 9.7 | 26.1 Years STANDARD_DEVIATION 5.6 | 26.8 Years STANDARD_DEVIATION 6.5 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 16 Participants | 64 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 12 | 3 / 12 | 5 / 12 | 4 / 12 | 5 / 16 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 16 |
Outcome results
Primary
Number of Participants With Investigator Defined Drug-related Adverse Events
Number of participants with investigator defined drug-related adverse events (AEs) is reported.
Time frame: From study drug administration until end-of-study examination, up to 77 days.
Population: Treated Set (TS): This subject set included all subjects who were documented to have taken study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 655064 Dose Group 1 - 80 mg | Number of Participants With Investigator Defined Drug-related Adverse Events | 2 Participants |
| BI 655064 Dose Group 2 - 120 mg | Number of Participants With Investigator Defined Drug-related Adverse Events | 1 Participants |
| BI 655064 Dose Group 3 - 180 mg | Number of Participants With Investigator Defined Drug-related Adverse Events | 4 Participants |
| BI 655064 Dose Group 4 - 240 mg | Number of Participants With Investigator Defined Drug-related Adverse Events | 2 Participants |
| Placebo Matching BI 655064 | Number of Participants With Investigator Defined Drug-related Adverse Events | 1 Participants |
Secondary
Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of the analyte BI 655064 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
Time frame: Within 3:00 hours:minutes (h:min) before and 08:00h, 12:00h, 24:00h, 36:00h, 48:00h, 72:00h, 96:00h, 108:00h, 120:00h, 168:00h, 264:00h, 432:00h, 648:00h, 984:00h, 1320:00h, 1656:00 h:min after BI 655064 administration.
Population: The pharmacokinetic (PK) set (PKS) included all subjects from the treated (TS) who provided at least 1 secondary PK endpoint that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation of PK endpoints. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 655064 Dose Group 1 - 80 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Chinese participants | 330 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 111 |
| BI 655064 Dose Group 1 - 80 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Japanese participants | 464 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 74.1 |
| BI 655064 Dose Group 2 - 120 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Japanese participants | 2020 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 78.8 |
| BI 655064 Dose Group 2 - 120 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Chinese participants | 1120 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 46.6 |
| BI 655064 Dose Group 3 - 180 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Chinese participants | 2910 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 60.1 |
| BI 655064 Dose Group 3 - 180 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Japanese participants | 6430 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 83.3 |
| BI 655064 Dose Group 4 - 240 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Chinese participants | 5610 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 59 |
| BI 655064 Dose Group 4 - 240 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Japanese participants | 7780 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 57.1 |
Comparison: Dose proportionality was explored using the power model. Dose proportionality of BI 655064 was to be assessed based on the exposure parameter AUC0-∞, determined for the 4 subcutaneous dose levels. This analysis is for the overall population.95% CI: [2.0993, 3.1073]
Secondary
Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz)
Area under the concentration-time curve of the analyte BI 655064 in the plasma over the time interval from 0 to the last measurable time point (AUC0-tz) is reported.
Time frame: Within 3:00 hours:minutes (h:min) before and 08:00h, 12:00h, 24:00h, 36:00h, 48:00h, 72:00h, 96:00h, 108:00h, 120:00h, 168:00h, 264:00h, 432:00h, 648:00h, 984:00h, 1320:00h, 1656:00 h:min after BI 655064 administration.
Population: The pharmacokinetic (PK) set (PKS) included all subjects from the treated set (TS) who provided at least 1 secondary PK endpoint that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation of PK endpoints. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 655064 Dose Group 1 - 80 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Chinese participants | 126 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 1740 |
| BI 655064 Dose Group 1 - 80 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Japanese participants | 365 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 165 |
| BI 655064 Dose Group 2 - 120 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Japanese participants | 2010 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 79.8 |
| BI 655064 Dose Group 2 - 120 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Chinese participants | 1110 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 47.2 |
| BI 655064 Dose Group 3 - 180 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Japanese participants | 6380 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 84.6 |
| BI 655064 Dose Group 3 - 180 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Chinese participants | 2900 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 60.4 |
| BI 655064 Dose Group 4 - 240 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Chinese participants | 5680 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 52.4 |
| BI 655064 Dose Group 4 - 240 mg | Area Under the Concentration-time Curve of the Analyte BI 655064 in the Plasma Over the Time Interval From 0 to the Last Measurable Time Point (AUC0-tz) | Japanese participants | 7750 microgram (µg)*hours (h)/mL | Geometric Coefficient of Variation 57.2 |
Comparison: Dose proportionality was explored using the power model. Dose proportionality of BI 655064 was to be assessed based on the exposure parameter AUC0-tz, determined for the 4 subcutaneous dose levels. This analysis is for the overall population.95% CI: [2.3395, 3.9187]
Secondary
Maximum Measured Concentration of BI 655064 in Plasma (Cmax)
Maximum measured concentration of BI 655064 in plasma (Cmax) is reported.
Time frame: Within 3:00 hours:minutes (h:min) before and 08:00h, 12:00h, 24:00h, 36:00h, 48:00h, 72:00h, 96:00h, 108:00h, 120:00h, 168:00h, 264:00h, 432:00h, 648:00h, 984:00h, 1320:00h, 1656:00 h:min after BI 655064 administration.
Population: The pharmacokinetic (PK) set (PKS) included all subjects from the treated set (TS) who provided at least 1 secondary PK endpoint that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation of PK endpoints. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 655064 Dose Group 1 - 80 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Chinese participants | 888 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 501 |
| BI 655064 Dose Group 1 - 80 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Japanese participants | 1550 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 315 |
| BI 655064 Dose Group 2 - 120 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Japanese participants | 7210 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 92.8 |
| BI 655064 Dose Group 2 - 120 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Chinese participants | 5160 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 51.6 |
| BI 655064 Dose Group 3 - 180 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Chinese participants | 8650 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 41.1 |
| BI 655064 Dose Group 3 - 180 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Japanese participants | 16300 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 73.6 |
| BI 655064 Dose Group 4 - 240 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Chinese participants | 15700 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 54.2 |
| BI 655064 Dose Group 4 - 240 mg | Maximum Measured Concentration of BI 655064 in Plasma (Cmax) | Japanese participants | 21300 nanogram (ng)/ (milliliter) mL | Geometric Coefficient of Variation 53.4 |
Comparison: Dose proportionality was explored using the power model. Dose proportionality of BI 655064 was to be assessed based on the exposure parameter Cmax, determined for the 4 subcutaneous dose levels. This analysis is for the overall population.95% CI: [1.7504, 3.1267]