Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate pharmacokinetics, including dose proportionality, following single intravenous and subcutaneous doses of spesolimab in healthy Chinese subjects.
Interventions
DRUGSpesolimap
Spesolimap
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female subjects (at least three subjects for each gender within each dose group) according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR), respiratory rate (RR), body temperature), 12-lead ECG, and clinical laboratory tests. * Chinese ethnicity, according to the following criteria: Ethnic Chinese, born in China and have 4 ethnic grandparents who were all born in China * Age of 18 to 45 years (inclusive) * Body weight ≥50 kg for male and ≥45 kg for female with body mass index (BMI) range ≥19 and \< 26 kg/m2 at visit 1 * Signed and dated written informed consent prior to admission to the trial, in accordance with GCP and local legislation * Female subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 16 weeks after trial completion \[c03320877-06\]: * Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the subject information * A vasectomised sexual partner (vasectomy at least one year prior to enrolment) * Surgically sterilised (including hysterectomy) * Postmenopausal, defined as at least one year of spontaneous amenorrhoea (in questionable cases a blood sample with simultaneous levels of follicle-stimulating hormone (FSH) above 40 U/L and estradiol below 30 mg/L is confirmatory)
Exclusion criteria
* Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to treatment or planned within 12 months after screening, e.g. hip replacement * Any finding in the medical examination (including BP, PR, RR, Body temperature or 12-lead ECG) deviating from normal and assessed as clinically relevant by the investigator * Repeated measurement of systolic BP outside the range of 90 to 140 mmHg, diastolic BP outside the range of 50 to 90 mmHg, or PR outside the range of 50 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 assessed 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 * Chronic or relevant acute infections including active and latent tuberculosis, human immunodeficiency virus (HIV) or viral hepatitis; QuantiFERON tuberculosis (TB) test will be performed at screening Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Spesolimap in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) before drug administration and SC: 30 minutes (min), IV: 1h 30 min, 2h, 3h, 4h, 8h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 504h, 672h, 840h, 1008h, 1344h, 1680h, 2184h, 2856h, 3528h, 4200h after drug administration. | Area under the concentration-time curve of Spesolimap in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis. The time frames differed slightly between intravenous (IV) and subcutaneous (SC) administration. The prefix 'IV' indicates when IV was measured only. The prefix 'SC' indicates when SC was measured only. No prefix means that measurement time points were identical for IV and SC administration. |
| Maximum Measured Concentration of the Spesolimap in Plasma (Cmax) | Within 3 hours (h) before drug administration and SC: 30 minutes (min), IV: 1h 30 min, 2h, 3h, 4h, 8h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 504h, 672h, 840h, 1008h, 1344h, 1680h, 2184h, 2856h, 3528h, 4200h after drug administration. | Maximum measured concentration of the Spesolimap in plasma (Cmax) The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis. Area under the concentration-time curve of Spesolimap in plasma over the time interval from 0 extrapolated to infinity (AUC0-8). The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis. The time frames differed slightly between intravenous (IV) and subcutaneous (SC) administration. The prefix 'IV' indicates when IV was measured only. The prefix 'SC' indicates when SC was measured only. No prefix means that measurement time points were identical for IV and SC administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AE)s | Frome day of drug administration until 16 weeks thereafter, up to 16 weeks. | Number of participants with treatment-emergent AEs. All AEs occurring between first drug administration until 16 weeks thereafter were assigned to the randomised treatment. |
| Number of Participants With Drug-related Adverse Events (AEs). | Frome day of drug administration until 16 weeks thereafter, up to 16 weeks. | Number of participants with drug-related AEs. All AEs occurring between first drug administration until 16 weeks thereafter were assigned to the randomised treatment. |
Countries
China
Participant flow
Recruitment details
This was an open-label parallel-group design for intravenous (IV) and subcutaneous (SC) single-dose administration of Spesolimap (BI 655130) in healthy Chinese male and female subjects. Three cohorts were dosed consecutively in ascending order within the IV and two cohorts within the SC dose groups.
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 |
|---|---|
| Spesolimap (BI 655130) - 450 Milligram (mg) - Intravenous (IV) A single dose of 450 mg Spesolimap was administered as solution for infusion intravenously over 90 minutes (mins) after an overnight fast. | 10 |
| Spesolimap - 900 mg - IV A single dose of 900 mg Spesolimap was administered as solution for infusion intravenously over 90 mins after an overnight fast. | 10 |
| Spesolimap - 1200 mg - IV A single dose of 1200 mg Spesolimap was administered as solution for infusion intravenously over 90 mins after an overnight fast. | 10 |
| Spesolimap - 300 mg - Subcutaneous (SC) A single dose of 300 mg Spesolimap was administered as solution for injection subcutaneously in the abdominal region within 60 seconds (s) after an overnight fast. | 10 |
| Spesolimap - 600 mg - SC A single dose of 600 mg Spesolimap was administered as solution for injection subcutaneously in the abdominal region within 60 s after an overnight fast. | 10 |
| Total | 50 |
Baseline characteristics
| Characteristic | Spesolimap (BI 655130) - 450 Milligram (mg) - Intravenous (IV) | Spesolimap - 900 mg - IV | Spesolimap - 1200 mg - IV | Spesolimap - 300 mg - Subcutaneous (SC) | Spesolimap - 600 mg - SC | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 29.0 Years STANDARD_DEVIATION 5.8 | 31.0 Years STANDARD_DEVIATION 7.8 | 34.6 Years STANDARD_DEVIATION 5.5 | 31.5 Years STANDARD_DEVIATION 6.5 | 30.5 Years STANDARD_DEVIATION 6.9 | 31.3 Years STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 50 Participants |
| Race (NIH/OMB) Black or African American | 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 30 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 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 8 / 10 | 9 / 10 | 8 / 10 | 7 / 10 | 9 / 10 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Area Under the Concentration-time Curve of Spesolimap in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of Spesolimap in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis. The time frames differed slightly between intravenous (IV) and subcutaneous (SC) administration. The prefix 'IV' indicates when IV was measured only. The prefix 'SC' indicates when SC was measured only. No prefix means that measurement time points were identical for IV and SC administration.
Time frame: Within 3 hours (h) before drug administration and SC: 30 minutes (min), IV: 1h 30 min, 2h, 3h, 4h, 8h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 504h, 672h, 840h, 1008h, 1344h, 1680h, 2184h, 2856h, 3528h, 4200h after drug administration.
Population: PK parameter analysis set (PKS): This set included all participants in the treated (TS) who provided at least one primary pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. PK data from replaced participants was expected to be not evaluable and thus replaced participants were not part of the PKS. One participant (900 mg IV group) missed the last measurement time point and was removed from the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Spesolimap (BI 655130) - 450 Milligram (mg) - Intravenous (IV) | Area Under the Concentration-time Curve of Spesolimap in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3380 Day times microgram per milliliter | Geometric Coefficient of Variation 17.5 |
| Spesolimap - 900 mg - IV | Area Under the Concentration-time Curve of Spesolimap in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 6960 Day times microgram per milliliter | Geometric Coefficient of Variation 19.2 |
| Spesolimap - 1200 mg - IV | Area Under the Concentration-time Curve of Spesolimap in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 10300 Day times microgram per milliliter | Geometric Coefficient of Variation 21.1 |
| Spesolimap - 300 mg - Subcutaneous (SC) | Area Under the Concentration-time Curve of Spesolimap in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1580 Day times microgram per milliliter | Geometric Coefficient of Variation 22.2 |
| Spesolimap - 600 mg - SC | Area Under the Concentration-time Curve of Spesolimap in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3260 Day times microgram per milliliter | Geometric Coefficient of Variation 34.1 |
Comparison: No statistical hypotheses tests were planned for this trial.90% CI: [0.979, 1.268]
Primary
Maximum Measured Concentration of the Spesolimap in Plasma (Cmax)
Maximum measured concentration of the Spesolimap in plasma (Cmax) The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis. Area under the concentration-time curve of Spesolimap in plasma over the time interval from 0 extrapolated to infinity (AUC0-8). The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis. The time frames differed slightly between intravenous (IV) and subcutaneous (SC) administration. The prefix 'IV' indicates when IV was measured only. The prefix 'SC' indicates when SC was measured only. No prefix means that measurement time points were identical for IV and SC administration.
Time frame: Within 3 hours (h) before drug administration and SC: 30 minutes (min), IV: 1h 30 min, 2h, 3h, 4h, 8h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 336h, 504h, 672h, 840h, 1008h, 1344h, 1680h, 2184h, 2856h, 3528h, 4200h after drug administration.
Population: PK parameter analysis set (PKS): This set included all participants in the treated (TS) who provided at least one primary pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. PK data from replaced participants was expected to be not evaluable and thus replaced participants were not part of the PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Spesolimap (BI 655130) - 450 Milligram (mg) - Intravenous (IV) | Maximum Measured Concentration of the Spesolimap in Plasma (Cmax) | 176 Microgram per milliliter | Geometric Coefficient of Variation 12.5 |
| Spesolimap - 900 mg - IV | Maximum Measured Concentration of the Spesolimap in Plasma (Cmax) | 370 Microgram per milliliter | Geometric Coefficient of Variation 15.1 |
| Spesolimap - 1200 mg - IV | Maximum Measured Concentration of the Spesolimap in Plasma (Cmax) | 504 Microgram per milliliter | Geometric Coefficient of Variation 17.3 |
| Spesolimap - 300 mg - Subcutaneous (SC) | Maximum Measured Concentration of the Spesolimap in Plasma (Cmax) | 32.0 Microgram per milliliter | Geometric Coefficient of Variation 16.8 |
| Spesolimap - 600 mg - SC | Maximum Measured Concentration of the Spesolimap in Plasma (Cmax) | 69.2 Microgram per milliliter | Geometric Coefficient of Variation 35.7 |
Comparison: No statistical hypotheses tests were planned for this trial.90% CI: [0.961, 1.183]
Secondary
Number of Participants With Drug-related Adverse Events (AEs).
Number of participants with drug-related AEs. All AEs occurring between first drug administration until 16 weeks thereafter were assigned to the randomised treatment.
Time frame: Frome day of drug administration until 16 weeks thereafter, up to 16 weeks.
Population: Treated set (TS): The treated set included all subjects who were treated with at least one dose of trial drug. The treatment assignment was determined based on the (first) treatment the subjects received. The treated set was used for safety analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimap (BI 655130) - 450 Milligram (mg) - Intravenous (IV) | Number of Participants With Drug-related Adverse Events (AEs). | 4 Participants |
| Spesolimap - 900 mg - IV | Number of Participants With Drug-related Adverse Events (AEs). | 8 Participants |
| Spesolimap - 1200 mg - IV | Number of Participants With Drug-related Adverse Events (AEs). | 4 Participants |
| Spesolimap - 300 mg - Subcutaneous (SC) | Number of Participants With Drug-related Adverse Events (AEs). | 4 Participants |
| Spesolimap - 600 mg - SC | Number of Participants With Drug-related Adverse Events (AEs). | 7 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (AE)s
Number of participants with treatment-emergent AEs. All AEs occurring between first drug administration until 16 weeks thereafter were assigned to the randomised treatment.
Time frame: Frome day of drug administration until 16 weeks thereafter, up to 16 weeks.
Population: Treated set (TS): The treated set included all subjects who were treated with at least one dose of trial drug. The treatment assignment was determined based on the (first) treatment the subjects received. The treated set was used for safety analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimap (BI 655130) - 450 Milligram (mg) - Intravenous (IV) | Number of Participants With Treatment-emergent Adverse Events (AE)s | 8 Participants |
| Spesolimap - 900 mg - IV | Number of Participants With Treatment-emergent Adverse Events (AE)s | 9 Participants |
| Spesolimap - 1200 mg - IV | Number of Participants With Treatment-emergent Adverse Events (AE)s | 8 Participants |
| Spesolimap - 300 mg - Subcutaneous (SC) | Number of Participants With Treatment-emergent Adverse Events (AE)s | 7 Participants |
| Spesolimap - 600 mg - SC | Number of Participants With Treatment-emergent Adverse Events (AE)s | 9 Participants |