Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the safety and tolerability of spesolimab following administration of single rising intravenous doses and single subcutaneous dose in healthy Japanese male volunteers. Secondary objective is the exploration of the pharmacokinetics including dose proportionality of spesolimab in healthy Japanese male volunteers.
Interventions
DRUGSpesolimab
single dose
DRUGPlacebo
single dose
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 male according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (Blood Pressure \[BP\], Pulse Rate \[PR\]), 12-lead Electrocardiogram \[ECG\], and clinical laboratory tests. * Japanese ethnicity, according to the following criteria: \-- born in Japan, have lived outside of Japan \<10 years, and have parents and grandparents who were all born in Japan * Age of 20 to 45 years (incl.) * Body Mass Index \[BMI\] of 18.5 to 25.0 kg/m2 (incl.) * Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation * Male subjects who agree to minimize the risk of female partners being pregnant by fulfilling any of the following criteria starting from the first administration of trial medication and until 30 days after trial completion: * Use of adequate contraception, e.g. any of the following methods plus condom: combined oral contraceptives, intrauterine device * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) * Surgically sterilised (including hysterectomy) female partner
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure \[BP\], Pulse Rate \[PR\] or Electrocardiogram \[ECG\]) 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 * Chronic or relevant acute infections including active tuberculosis, HIV or viral hepatitis; QuantiFERON TB test will be performed at screening. * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation) * Participation in another trial where an investigational drug has been administered within 5 half-lives prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug. * Administered live vaccine within 6 weeks prior to randomisation or Have plans for administration of live vaccines during the study period. * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) * Inability to refrain from smoking on specified trial days * Alcohol abuse (consumption of more than 30 g per day) * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial * Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial * Inability to comply with dietary regimen of trial site * A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant Electrocardiogram \[ECG\] finding at screening * A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Drug-related Adverse Events (AEs) | From first drug administration until the end of trial examination, up to 151 days. | The primary endpoint is to assess safety and tolerability of spesolimab as the number \[N\] of subjects with drug-related AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Up to 3528 hours after administration of spesolimab. | AUC0-∞, Area under the concentration-time curve of spesolimab in plasma over the time interval from 0 extrapolated to infinity is presented. Pharmacokinetic samples were collected within 2 hours pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with intravenous administration of spesolimab. Pharmacokinetic samples were collected within 2 hours pre-dose and at 0.5, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with subcutaneous administration of spesolimab. |
| Maximum Measured Concentration of Spesolimab in Plasma (Cmax) | Up to 3528 hours after administration of spesolimab. | Cmax, maximum measured concentration of spesolimab in plasma is presented. Pharmacokinetic samples were collected within 2 hours pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with intravenous administration of Up to 3528 hours after administration of spesolimab. Pharmacokinetic samples were collected within 2 hours pre-dose and at 0.5, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with subcutaneous administration of spesolimab. |
| Total Clearance of Spesolimab in Plasma After Intravenous Administration (CL) | Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab. | CL, total clearance of spesolimab in plasma after intravenous administration is presented for intravenous dose groups. |
| Volume of Distribution at Steady State After Intravenous Administration of Spesolimab (Vss) | Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab. | Vss, volume of distribution at steady state after intravenous administration of spesolimab is presented for intravenous dose groups. |
Countries
South Korea
Participant flow
Recruitment details
This was a double-blind, randomised, and placebo-controlled trial of single rising intravenous (IV) doses and single subcutaneous (SC) doses of spesolimab (BI 655130) in healthy male Japanese subjects.
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were not met. Dose level for each arm cannot be provided because the information is a combination of both commercially sensitive confidential information as well as proprietary information.
Participants by arm
| Arm | Count |
|---|---|
| Spesolimab Low Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2. | 6 |
| Spesolimab Medium Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2. | 6 |
| Spesolimab High Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2. | 6 |
| Spesolimab Low Dose Group (Subcutaneous) Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2. | 6 |
| Placebo Matching to Spesolimab Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2. | 8 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Spesolimab Low Dose Group (Intravenous) | Total | Placebo Matching to Spesolimab | Spesolimab Low Dose Group (Subcutaneous) | Spesolimab High Dose Group (Intravenous) | Spesolimab Medium Dose Group (Intravenous) |
|---|---|---|---|---|---|---|
| Age, Continuous | 31.5 Years STANDARD_DEVIATION 4.51 | 33.0 Years STANDARD_DEVIATION 5.61 | 31.4 Years STANDARD_DEVIATION 7.65 | 34.7 Years STANDARD_DEVIATION 5.24 | 36.7 Years STANDARD_DEVIATION 3.56 | 31.5 Years STANDARD_DEVIATION 4.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 32 Participants | 8 Participants | 6 Participants | 6 Participants | 6 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 32 Participants | 8 Participants | 6 Participants | 6 Participants | 6 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 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 1 / 6 | 1 / 6 | 1 / 6 | 0 / 6 | 2 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Number of Subjects With Drug-related Adverse Events (AEs)
The primary endpoint is to assess safety and tolerability of spesolimab as the number \[N\] of subjects with drug-related AEs.
Time frame: From first drug administration until the end of trial examination, up to 151 days.
Population: Treated set (TS): TS includes all subjects dispensed trial medication and documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimab Low Dose Group (Intravenous) | Number of Subjects With Drug-related Adverse Events (AEs) | 0 Participants |
| Spesolimab Medium Dose Group (Intravenous) | Number of Subjects With Drug-related Adverse Events (AEs) | 0 Participants |
| Spesolimab High Dose Group (Intravenous) | Number of Subjects With Drug-related Adverse Events (AEs) | 0 Participants |
| Spesolimab Low Dose Group (Subcutaneous) | Number of Subjects With Drug-related Adverse Events (AEs) | 0 Participants |
| Placebo Matching to Spesolimab | Number of Subjects With Drug-related Adverse Events (AEs) | 0 Participants |
Secondary
Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞, Area under the concentration-time curve of spesolimab in plasma over the time interval from 0 extrapolated to infinity is presented. Pharmacokinetic samples were collected within 2 hours pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with intravenous administration of spesolimab. Pharmacokinetic samples were collected within 2 hours pre-dose and at 0.5, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with subcutaneous administration of spesolimab.
Time frame: Up to 3528 hours after administration of spesolimab.
Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Spesolimab Low Dose Group (Intravenous) | Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1890 Day*microgram/millilitre [day∙μg/mL] | Geometric Coefficient of Variation 19.9 |
| Spesolimab Medium Dose Group (Intravenous) | Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3930 Day*microgram/millilitre [day∙μg/mL] | Geometric Coefficient of Variation 18.4 |
| Spesolimab High Dose Group (Intravenous) | Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 7060 Day*microgram/millilitre [day∙μg/mL] | Geometric Coefficient of Variation 18 |
| Spesolimab Low Dose Group (Subcutaneous) | Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1390 Day*microgram/millilitre [day∙μg/mL] | Geometric Coefficient of Variation 24.8 |
Comparison: Dose proportionality was explored using the power model. Dose proportionality of spesolimab was to be assessed based on the exposure parameter AUC0-∞, determined for the 3 intravenous dose levels (perfect dose proportionality would correspond to a slope of 1).95% CI: [0.781, 1.1256]
Secondary
Maximum Measured Concentration of Spesolimab in Plasma (Cmax)
Cmax, maximum measured concentration of spesolimab in plasma is presented. Pharmacokinetic samples were collected within 2 hours pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with intravenous administration of Up to 3528 hours after administration of spesolimab. Pharmacokinetic samples were collected within 2 hours pre-dose and at 0.5, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with subcutaneous administration of spesolimab.
Time frame: Up to 3528 hours after administration of spesolimab.
Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Spesolimab Low Dose Group (Intravenous) | Maximum Measured Concentration of Spesolimab in Plasma (Cmax) | 99.7 Microgram/millilitre [μg/mL] | Geometric Coefficient of Variation 10.4 |
| Spesolimab Medium Dose Group (Intravenous) | Maximum Measured Concentration of Spesolimab in Plasma (Cmax) | 193.0 Microgram/millilitre [μg/mL] | Geometric Coefficient of Variation 17.9 |
| Spesolimab High Dose Group (Intravenous) | Maximum Measured Concentration of Spesolimab in Plasma (Cmax) | 400.0 Microgram/millilitre [μg/mL] | Geometric Coefficient of Variation 12.9 |
| Spesolimab Low Dose Group (Subcutaneous) | Maximum Measured Concentration of Spesolimab in Plasma (Cmax) | 32.2 Microgram/millilitre [μg/mL] | Geometric Coefficient of Variation 21.8 |
Comparison: Dose proportionality was explored using the power model. Dose proportionality of spesolimab was to be assessed based on the exposure parameter Cmax, determined for the 3 intravenous dose levels (perfect dose proportionality would correspond to a slope of 1).95% CI: [0.8809, 1.1219]
Secondary
Total Clearance of Spesolimab in Plasma After Intravenous Administration (CL)
CL, total clearance of spesolimab in plasma after intravenous administration is presented for intravenous dose groups.
Time frame: Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab.
Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Spesolimab Low Dose Group (Intravenous) | Total Clearance of Spesolimab in Plasma After Intravenous Administration (CL) | 0.159 Litre/day [L/day] | Geometric Coefficient of Variation 19.9 |
| Spesolimab Medium Dose Group (Intravenous) | Total Clearance of Spesolimab in Plasma After Intravenous Administration (CL) | 0.153 Litre/day [L/day] | Geometric Coefficient of Variation 18.4 |
| Spesolimab High Dose Group (Intravenous) | Total Clearance of Spesolimab in Plasma After Intravenous Administration (CL) | 0.170 Litre/day [L/day] | Geometric Coefficient of Variation 18 |
Secondary
Volume of Distribution at Steady State After Intravenous Administration of Spesolimab (Vss)
Vss, volume of distribution at steady state after intravenous administration of spesolimab is presented for intravenous dose groups.
Time frame: Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab.
Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Spesolimab Low Dose Group (Intravenous) | Volume of Distribution at Steady State After Intravenous Administration of Spesolimab (Vss) | 6.19 Litre [L] | Geometric Coefficient of Variation 18.1 |
| Spesolimab Medium Dose Group (Intravenous) | Volume of Distribution at Steady State After Intravenous Administration of Spesolimab (Vss) | 6.97 Litre [L] | Geometric Coefficient of Variation 11.9 |
| Spesolimab High Dose Group (Intravenous) | Volume of Distribution at Steady State After Intravenous Administration of Spesolimab (Vss) | 6.60 Litre [L] | Geometric Coefficient of Variation 11.6 |