Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the relative bioavailability of BI 655130 following subcutaneous administration (Test, T) compared to BI 655130 following intravenous infusion (Reference, R). The secondary objective is the evaluation and comparison of several pharmacokinetic parameters between all tested treatments.
Interventions
DRUGBI 655130
single dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female 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 (Body Mass Index) 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 (Good Clinical Practice) and local legislation * Male subjects, or female subjects who meet any of the following criteria starting from at least 30 days before 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: implants, injectables, combined oral or vaginal contraceptives, intrauterine device * Sexually abstinent * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) * Surgically sterilised (including hysterectomy) * Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)
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 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 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 * 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 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug * 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 20 g per day for females and 30 g per day for males) * 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 repeatedly greater than 470 ms in females) or any other relevant 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 Female subjects will not be allowed to participate if any of the following applies: * Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion * Lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 655130 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Pharmacokinetic samples were collected at pre-dose and at 0.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration. | AUC0-tz, area under the concentration-time curve of BI 655130 in plasma over the time interval from 0 to the last quantifiable data point is presented. As defined in the statistical analysis plan, this outcome measure was analysed for comparison of subcutaneous (SC) versus intravenous (IV) administration of BI 655130 high dose as part of the primary analysis. |
| Maximum Measured Concentration of BI 655130 in Plasma (Cmax) | Pharmacokinetic samples were collected at pre-dose and at 0.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration. | Cmax, maximum measured concentration of BI 655130 in plasma is presented. As defined in the statistical analysis plan, this outcome measure was analysed for comparison of subcutaneous (SC) versus intravenous (IV) administration of BI 655130 high dose as part of the primary analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Pharmacokinetic samples were collected at pre-dose and at 0.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 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 BI 655130 in plasma over the time interval from 0 extrapolated to infinity is presented. As defined in the statistical analysis plan, this outcome measure was analysed for comparison of subcutaneous (SC) versus intravenous (IV) administration of BI 655130 high dose as part of the primary analysis. |
Countries
Belgium
Participant flow
Recruitment details
This was an open-label, parallel group trial investigating two different dose strengths of a single subcutaneous (SC) dose of BI 655130 and one single intravenous (IV) dose of BI 655130.
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 entered to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| BI 655130 Low Dose SC Subject received single low dose BI 655130 solution as subcutaneous (SC) injection on day 1. | 12 |
| BI 655130 High Dose SC Subject received single high dose BI 655130 solution as subcutaneous (SC) injection on day 1. | 12 |
| BI 655130 High Dose IV Subject received single high dose BI 655130 solution as 30 minutes intravenous (IV) infusion on day 1. | 12 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | BI 655130 High Dose IV | Total | BI 655130 Low Dose SC | BI 655130 High Dose SC |
|---|---|---|---|---|
| Age, Continuous | 38.6 Years STANDARD_DEVIATION 10.7 | 38.4 Years STANDARD_DEVIATION 9.2 | 42.3 Years STANDARD_DEVIATION 7.5 | 34.3 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 35 Participants | 12 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 36 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Female | 11 Participants | 33 Participants | 11 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 8 / 12 | 11 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 655130 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 655130 in plasma over the time interval from 0 to the last quantifiable data point is presented. As defined in the statistical analysis plan, this outcome measure was analysed for comparison of subcutaneous (SC) versus intravenous (IV) administration of BI 655130 high dose as part of the primary analysis.
Time frame: Pharmacokinetic samples were collected at pre-dose and at 0.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration.
Population: Pharmacokinetic (PK) analysis set (PKS) restricted to high dose BI 655130 administration for primary analyses of the primary and secondary outcomes: All subjects of the Treated Set who were administered with BI 655130 high dose treatment and provided at least 1 observation for at least 1 primary or secondary PK endpoint that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 655130 High Dose SC | Area Under the Concentration-time Curve of BI 655130 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 1579.19 Day*microgram/millilitre [day*μg/mL] |
| BI 655130 High Dose IV | Area Under the Concentration-time Curve of BI 655130 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2204.35 Day*microgram/millilitre [day*μg/mL] |
90% CI: [60.57, 84.73]
Primary
Maximum Measured Concentration of BI 655130 in Plasma (Cmax)
Cmax, maximum measured concentration of BI 655130 in plasma is presented. As defined in the statistical analysis plan, this outcome measure was analysed for comparison of subcutaneous (SC) versus intravenous (IV) administration of BI 655130 high dose as part of the primary analysis.
Time frame: Pharmacokinetic samples were collected at pre-dose and at 0.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration.
Population: Pharmacokinetic (PK) analysis set (PKS) restricted to high dose BI 655130 administration for primary analyses of the primary and secondary outcomes: All subjects of the Treated Set who were administered with BI 655130 high dose treatment and provided at least 1 observation for at least 1 primary or secondary PK endpoint that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 655130 High Dose SC | Maximum Measured Concentration of BI 655130 in Plasma (Cmax) | 33.36 Microgram/millilitre [μg/mL] |
| BI 655130 High Dose IV | Maximum Measured Concentration of BI 655130 in Plasma (Cmax) | 113.90 Microgram/millilitre [μg/mL] |
90% CI: [24.27, 35.35]
Secondary
Area Under the Concentration-time Curve of BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞, area under the concentration-time curve of BI 655130 in plasma over the time interval from 0 extrapolated to infinity is presented. As defined in the statistical analysis plan, this outcome measure was analysed for comparison of subcutaneous (SC) versus intravenous (IV) administration of BI 655130 high dose as part of the primary analysis.
Time frame: Pharmacokinetic samples were collected at pre-dose and at 0.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration.
Population: Pharmacokinetic (PK) analysis set (PKS) restricted to high dose BI 655130 administration for primary analyses of the primary and secondary outcomes: All subjects of the Treated Set who were administered with BI 655130 high dose treatment and provided at least 1 observation for at least 1 primary or secondary PK endpoint that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 655130 High Dose SC | Area Under the Concentration-time Curve of BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1600.92 Day*microgram/millilitre [day*μg/mL] |
| BI 655130 High Dose IV | Area Under the Concentration-time Curve of BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2279.94 Day*microgram/millilitre [day*μg/mL] |
90% CI: [59.26, 83.2]