Healthy
Conditions
Brief summary
This trial will investigate the pharmacokinetics, safety and tolerability of BI 695501 and to establish pharmacokinetic equivalence of BI 695501 to adalimumab.
Interventions
DRUGadalimumab
40mg adalimumab single s.c. injection
DRUGBI695501
BI 695501 single s.c injection
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males 2. Body mass index (BMI) =18.5 to =29.9 kg/m2
Exclusion criteria
1. Any clinically relevant abnormal finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant previous or concomitant disease as judged by the investigator. 3. Chronic or relevant acute infections. A negative result for Human Immunodeficiency Virus, Hepatitis B and Hepatitis C testing is required for participation. 4. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 5. Intake of prescribed or over-the-counter drugs with a long half-life (\>24 hours) within at least one month or less than 5 half-lives of the respective drug prior to administration or during the trial 6. Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day) 7. Inability to refrain from smoking during days of confinement at the study center 8. Alcohol abuse (average more than 30 g/day) 9. Current drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h 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-∞). Geometric mean and geometric coefficient of variation (gCV) are provided as descriptive statistic. |
| Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) | 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration | Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz). Geometric mean and geometric coefficient of variation (gCV) are provided as descriptive statistic. |
| Maximum Measured Concentration of the BI 695501 in Plasma (Cmax) | 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration | Maximum measured concentration of the BI 695501 in plasma (Cmax). Geometric mean and geometric coefficient of variation (gCV) are provided as descriptive statistic. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half- Life of the BI 695501 in Plasma (t1/2) | 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration | Terminal half- life of the BI 695501 in plasma (t1/2). |
| Apparent Clearance of the BI 695501 in the Plasma After Extra-vascular Administration (CL/F) | 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration | Apparent clearance of the BI 695501 in the plasma after extra-vascular administration (CL/F). |
Countries
New Zealand
Participant flow
Recruitment details
This was phase I, open-label, randomised, parallel-arm, single-dose, active -comparator study with healthy subjects.
Pre-assignment details
Subjects were screened for eligibility to participate in the trial. They attended a specialist sites which ensured strict implementation of inclusion/exclusion criteria and they were not to be entered in trial if any one of the specific entry criteria was violated. They were free to withdraw their consent at any time without penalty or prejudice.
Participants by arm
| Arm | Count |
|---|---|
| BI 695501 Subject received one subcutaneous injection via prefilled syringe containing 40 milligram (mg) /0.8 milliliter (mL) BI 695501 | 67 |
| Humira®US Subject received one subcutaneous injection via prefilled syringe containing 40 milligram (mg) /0.8 milliliter (mL) Humira®US | 62 |
| Humira®EU Subject received one subcutaneous injection via prefilled syringe containing 40 milligram (mg) /0.8 milliliter (mL) Humira®EU | 64 |
| Total | 193 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Other reason not listed | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 4 |
Baseline characteristics
| Characteristic | BI 695501 | Humira®US | Humira®EU | Total |
|---|---|---|---|---|
| Age, Continuous | 26.3 Years STANDARD_DEVIATION 8.2 | 24.4 Years STANDARD_DEVIATION 6.6 | 27.6 Years STANDARD_DEVIATION 8.9 | 26.1 Years STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 7 Participants | 7 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 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 | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 56 Participants | 51 Participants | 55 Participants | 162 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 67 Participants | 62 Participants | 64 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 62 | 0 / 64 |
| other Total, other adverse events | 35 / 67 | 29 / 62 | 33 / 64 |
| serious Total, serious adverse events | 0 / 67 | 0 / 62 | 0 / 64 |
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-∞)
Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Geometric mean and geometric coefficient of variation (gCV) are provided as descriptive statistic.
Time frame: 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration
Population: Pharmacokinetic set (PKS): This set included all subjects of the randomized and treated set who in addition provided at least one Pharmacokinetic (PK) endpoint and had no important protocol violations relevant to the evaluation of bio-equivalence.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2740 Micro-gram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 48.2 |
| Humira®US | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2390 Micro-gram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 44.3 |
| Humira®EU | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2050 Micro-gram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 53.2 |
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.116390% CI: [98.752, 129.812]ANOVA
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.734590% CI: [113.984, 153.412]ANOVA
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.183390% CI: [74.974, 99.83]ANOVA
Primary
Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz). Geometric mean and geometric coefficient of variation (gCV) are provided as descriptive statistic.
Time frame: 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration
Population: Pharmacokinetic set (PKS): This set included all subjects of the randomized and treated set who in addition provided at least one Pharmacokinetic (PK) endpoint and had no important protocol violations relevant to the evaluation of bio-equivalence.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) | 2480 Micro-gram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 40 |
| Humira®US | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) | 2250 Micro-gram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 37.7 |
| Humira®EU | Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) | 1890 Micro-gram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 46.1 |
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.030390% CI: [97.384, 122.935]ANOVA
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.654790% CI: [113.492, 146.365]ANOVA
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.157290% CI: [76.238, 97.564]ANOVA
Primary
Maximum Measured Concentration of the BI 695501 in Plasma (Cmax)
Maximum measured concentration of the BI 695501 in plasma (Cmax). Geometric mean and geometric coefficient of variation (gCV) are provided as descriptive statistic.
Time frame: 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration
Population: Pharmacokinetic set (PKS): This set included all subjects of the randomized and treated set who in addition provided at least one Pharmacokinetic (PK) endpoint and had no important protocol violations relevant to the evaluation of bio-equivalence.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 | Maximum Measured Concentration of the BI 695501 in Plasma (Cmax) | 4.47 Micro-gram/milliliter (μg/mL) | Geometric Coefficient of Variation 34.2 |
| Humira®US | Maximum Measured Concentration of the BI 695501 in Plasma (Cmax) | 4.07 Micro-gram/milliliter (μg/mL) | Geometric Coefficient of Variation 34.2 |
| Humira®EU | Maximum Measured Concentration of the BI 695501 in Plasma (Cmax) | 3.74 Micro-gram/milliliter (μg/mL) | Geometric Coefficient of Variation 40.5 |
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.021290% CI: [99.687, 122.035]ANOVA
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.1790% CI: [105.638, 130.757]ANOVA
Comparison: ANOVA (analysis of variance) model on the logarithm scale was used with 'treatment' and 'age' as fixed effect.p-value: 0.001690% CI: [87.064, 107.017]ANOVA
Secondary
Apparent Clearance of the BI 695501 in the Plasma After Extra-vascular Administration (CL/F)
Apparent clearance of the BI 695501 in the plasma after extra-vascular administration (CL/F).
Time frame: 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration
Population: Pharmacokinetic set (PKS): This set included all subjects of the randomized and treated set who in addition provided at least one Pharmacokinetic (PK) endpoint and had no important protocol violations relevant to the evaluation of bio-equivalence.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 | Apparent Clearance of the BI 695501 in the Plasma After Extra-vascular Administration (CL/F) | 0.244 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 48.2 |
| Humira®US | Apparent Clearance of the BI 695501 in the Plasma After Extra-vascular Administration (CL/F) | 0.279 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 44.3 |
| Humira®EU | Apparent Clearance of the BI 695501 in the Plasma After Extra-vascular Administration (CL/F) | 0.326 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 53.2 |
Secondary
Terminal Half- Life of the BI 695501 in Plasma (t1/2)
Terminal half- life of the BI 695501 in plasma (t1/2).
Time frame: 1 hour (h) before drug administration and 1, 4, 8, 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 816, 1032, 1320, 1704 h after drug administration
Population: Pharmacokinetic set (PKS): This set included all subjects of the randomized and treated set who in addition provided at least one Pharmacokinetic (PK) endpoint and had no important protocol violations relevant to the evaluation of bio-equivalence.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 | Terminal Half- Life of the BI 695501 in Plasma (t1/2) | 292 hour | Geometric Coefficient of Variation 104 |
| Humira®US | Terminal Half- Life of the BI 695501 in Plasma (t1/2) | 230 hour | Geometric Coefficient of Variation 76.8 |
| Humira®EU | Terminal Half- Life of the BI 695501 in Plasma (t1/2) | 236 hour | Geometric Coefficient of Variation 98.3 |