Healthy
Conditions
Brief summary
To investigate and compare the pharmacokinetics, safety and tolerability of BI 695501 administered subcutaneously via prefilled syringe or autoinjector
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male, non-athletic\* Caucasian subjects 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 ECG, and clinical laboratory tests. * Age between 18 and 65 years (inclusive) * BMI of 18 to 30 kg/m2 (inclusive) * BMI 18 to \<20, or * BMI 20 to \<25, or * BMI 25 to \<=30 * Signed and dated written informed consent prior to admission to the trial in accordance with Good Clinical Practice (GCP) and local legislation. * Subjects agree to use an acceptable method of contraception during the trial and for 6 month after the dose of trial drug. * Non-athletic defined as person performing no more than one hour of exercise per week
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) that deviates from normal and judged as clinically relevant by the investigator. * Any evidence of a concomitant disease judged as clinically relevant by the investigator including gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal disorders or 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. * Positive result for HIV, HBV, and hepatitis C (Hep C) at screening. * History of relevant allergy or hypersensitivity including allergy to the trial medication, its excipients or device materials (e.g. natural rubber or latex). * Intake of drugs with a long half-life (more than 24 hours) within 30 days or less than 5 half-lives of the respective drug prior to administration of trial medication. * Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial. * Previous exposure to a biologic drug. * Intake of an investigational drug in another trial within 2 months prior to intake of trial medication in this trial or intake of an investigational drug during the course of this trial. * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day). * Inability to refrain from smoking during days of confinement at the trial site. * Alcohol abuse (consumption of more than 4 units/day). * Unwillingness/inability to refrain from intake of alcoholic beverages from 48 hours prior to the trial medication administration and until Day 14 post trial medication administration; and/or to limit alcohol intake to a maximum of 3 units per day until e.o.t. * 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 1 week prior to administration of trial medication or contact sport during the entire trial and unwilling to avoid vigorous exercise for 14 days post dosing. * Inability to comply with dietary regimen of trial site. * Any out-of-range laboratory values considered clinically significant by the investigator; subjects with creatine kinase (CK) values 2 times the upper limit of normal (ULN) at Day -1 are excluded from participation. * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because he is considered not able to understand and comply with trial requirements, or has a condition that would not allow safe participation in the trial. * Subjects with any immunological disorders or auto-immune disorders, (e.g., RA, lupus erythematosus, scleroderma, etc.). * Subject has received a live vaccine within 12 weeks prior to enrolling in the trial. * History of TB or positive finding in IGRA. * Evidence of skin irritation or infection at the planned injection place.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 695501 in Plasma (Cmax) | PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration. | Maximum measured concentration of BI 695501 in plasma (Cmax). The rate and extent of absorption of BI 695501 by assessment of maximum plasma concentration following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results. |
| Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to 1032 Hours After Dose (AUC0-1032) | PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration. | Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 to 1032 hours after dose (AUC0-1032). The rate and extent of absorption of BI 695501 by assessment of AUC0-1032 following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results. |
| Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration. | Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) based on observed concentration at time of last measurable concentration. The rate and extent of absorption of BI 695501 by assessment of (AUC0-∞) following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Drug-related Adverse Events (AEs) | From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period | Number of subjects with drug-related Adverse Events (AEs). Any event with an onset after the administration of the trial medication up to a period of 70 days was defined as a treatment-emergent AE (TEAE). A treatment-related AE was defined as any TEAE assessed by the investigator as related to the trial medication. |
Countries
Belgium
Participant flow
Pre-assignment details
This was randomized, single-dose, parallel-arm, open-label Phase I trial with healthy male subjects.
Participants by arm
| Arm | Count |
|---|---|
| BI 695501 Autoinjector (AI) Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product) | 35 |
| BI 695501 Pre-filled Syringe (PFS) Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product) | 36 |
| Total | 71 |
Baseline characteristics
| Characteristic | BI 695501 Autoinjector (AI) | BI 695501 Pre-filled Syringe (PFS) | Total |
|---|---|---|---|
| Age, Continuous | 39.3 Years STANDARD_DEVIATION 13.77 | 40.1 Years STANDARD_DEVIATION 13.32 | 39.7 Years STANDARD_DEVIATION 13.45 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 36 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 35 | 23 / 36 |
| serious Total, serious adverse events | 0 / 35 | 0 / 36 |
Outcome results
Primary
Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)
Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) based on observed concentration at time of last measurable concentration. The rate and extent of absorption of BI 695501 by assessment of (AUC0-∞) following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.
Time frame: PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.
Population: Pharmacokinetic analysis set (PKS): The PKS consisted of all randomized subjects who received the single dose of trial medication, had at least one evaluable primary pharmacokinetic parameter, and were without important protocol deviations or violations thought to significantly affect the pharmacokinetics of BI 695501.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 Autoinjector (AI) | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 2080 μg*h/mL | Geometric Coefficient of Variation 58.2 |
| BI 695501 Pre-filled Syringe (PFS) | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 2110 μg*h/mL | Geometric Coefficient of Variation 58 |
Comparison: Analysis of variance (ANOVA) model on the log scale was used including treatment and BMI group as fixed effects90% CI: [82.13, 122.29]ANOVA
Primary
Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to 1032 Hours After Dose (AUC0-1032)
Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 to 1032 hours after dose (AUC0-1032). The rate and extent of absorption of BI 695501 by assessment of AUC0-1032 following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.
Time frame: PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.
Population: Pharmacokinetic analysis set (PKS): The PKS consisted of all randomized subjects who received the single dose of trial medication, had at least one evaluable primary pharmacokinetic parameter, and were without important protocol deviations or violations thought to significantly affect the pharmacokinetics of BI 695501.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 Autoinjector (AI) | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to 1032 Hours After Dose (AUC0-1032) | 1810 μg*h/mL | Geometric Coefficient of Variation 47.5 |
| BI 695501 Pre-filled Syringe (PFS) | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to 1032 Hours After Dose (AUC0-1032) | 1840 μg*h/mL | Geometric Coefficient of Variation 47.1 |
Comparison: Analysis of variance (ANOVA) model on the log scale was used including treatment and BMI group as fixed effects90% CI: [85.15, 117.76]ANOVA
Primary
Maximum Measured Concentration of BI 695501 in Plasma (Cmax)
Maximum measured concentration of BI 695501 in plasma (Cmax). The rate and extent of absorption of BI 695501 by assessment of maximum plasma concentration following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.
Time frame: PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.
Population: Pharmacokinetic analysis set (PKS): The PKS consisted of all randomized subjects who received the single dose of trial medication, had at least one evaluable primary pharmacokinetic parameter, and were without important protocol deviations or violations thought to significantly affect the pharmacokinetics of BI 695501.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 Autoinjector (AI) | Maximum Measured Concentration of BI 695501 in Plasma (Cmax) | 3.79 Micro-gram (µg) per milliliter (mL) | Geometric Coefficient of Variation 27.4 |
| BI 695501 Pre-filled Syringe (PFS) | Maximum Measured Concentration of BI 695501 in Plasma (Cmax) | 3.48 Micro-gram (µg) per milliliter (mL) | Geometric Coefficient of Variation 51 |
Comparison: Analysis of variance (ANOVA) model on the log scale was used including treatment and body mass index (BMI) group as fixed effects90% CI: [96.8, 125.44]ANOVA
Secondary
Number of Subjects With Drug-related Adverse Events (AEs)
Number of subjects with drug-related Adverse Events (AEs). Any event with an onset after the administration of the trial medication up to a period of 70 days was defined as a treatment-emergent AE (TEAE). A treatment-related AE was defined as any TEAE assessed by the investigator as related to the trial medication.
Time frame: From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period
Population: Safety analysis set (SAF): The SAF consisted of all subjects in the enrolled set who received at least one dose of trial medication and subjects were classified according to treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 695501 Autoinjector (AI) | Number of Subjects With Drug-related Adverse Events (AEs) | 20 Number of Subjects |
| BI 695501 Pre-filled Syringe (PFS) | Number of Subjects With Drug-related Adverse Events (AEs) | 16 Number of Subjects |