Healthy
Conditions
Brief summary
The main objective of this trial is to compare the pharmacokinetics (PK) of 40 mg BI 695501 100 mg/mL with 40 mg BI 695501 50 mg/mL following single subcutaneous administration.
Interventions
DRUGBI 695501 - higher concentration
BI 695501 - higher concentration
DRUGBI 695501 - lower concentration
BI 695501 - lower concentration
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests. * Age of 18 to 55 years (inclusive). * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive). * Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. * Participants of reproductive potential (childbearing potential1) must be willing and able to use highly effective methods of birth control per International Council for Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year from at least 30 days before administration of the trial medication until 30 days after trial completion.
Exclusion criteria
* Previous exposure to adalimumab or proposed adalimumab biosimilar drugs. * Any finding in the medical examination (including blood pressure (BP), pulse rate (PR) or electrocardiogram (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 human immunodeficiency virus (HIV), hepatitis B virus (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). * Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 to 1344 Hours After Dose Administration (AUC0-1344) | BI 695501 was measured within 1 hour before and 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration. | Area under the concentration-time curve of BI 695501 in plasma over the time interval from 0 to 1344 hours after dose administration (AUC0-1344). The presented means are adjusted based on analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment, location of trial medication injection and baseline body weight. |
| Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | BI 695501 was measured within 1 hour before and 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration. | Area under the concentration-time curve of BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The presented means are adjusted based on analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment, location of trial medication injection and baseline body weight. |
| Maximum Measured Concentration of BI 695501 in Plasma (Cmax) | BI 695501 was measured within 1 hour before and 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration. | Maximum measured concentration of BI 695501 in plasma (Cmax). The presented means are adjusted based on analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment, location of trial medication injection and baseline body weight. |
Countries
United States
Participant flow
Recruitment details
This was a 14-week, randomized, single dose, parallel arm, double blind, Phase I trial in healthy male and female subjects aged ≥18 to ≤55 years. The aim of this trial was to evaluate and compare the pharmacokinetics (PK), safety, tolerability, and immunogenicity of the test treatment to the reference treatment administered subcutaneously via prefilled syringe (PFS).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trials. There was no run-in period and subjects did not have to attend a specialist site. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| BI 695501 40 mg/0.4 mL (T) Participants were subcutaneously injected 40 milligram (mg)/0.4 milliliter (mL) of BI 695501 solution for injection in prefilled syringe (PFS) (Test Treatment (T)). | 99 |
| BI 695501 40 mg/0.8 mL (R) Participants were subcutaneously injected 40 milligrams (mg)/0.8 milliliter (mL) of BI 695501 solution for injection in prefilled syringe (PFS) (Reference Treatment (R)). | 101 |
| Total | 200 |
Baseline characteristics
| Characteristic | BI 695501 40 mg/0.8 mL (R) | Total | BI 695501 40 mg/0.4 mL (T) |
|---|---|---|---|
| Age, Continuous | 37.5 Years STANDARD_DEVIATION 8.41 | 37.0 Years STANDARD_DEVIATION 9.13 | 36.4 Years STANDARD_DEVIATION 9.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants | 106 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 94 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 93 Participants | 183 Participants | 90 Participants |
| Sex: Female, Male Female | 47 Participants | 104 Participants | 57 Participants |
| Sex: Female, Male Male | 54 Participants | 96 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 99 | 0 / 101 |
| other Total, other adverse events | 6 / 99 | 13 / 101 |
| serious Total, serious adverse events | 0 / 99 | 0 / 101 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The presented means are adjusted based on analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment, location of trial medication injection and baseline body weight.
Time frame: BI 695501 was measured within 1 hour before and 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration.
Population: Pharmacokinetic analysis set (PKS): The pharmacokinetic set consisted of all randomized subjects who received the single dose of trial medication, and had at least one evaluable primary pharmacokinetics (PK) parameter, and were without important protocol deviations or violations thought to have a relevant impact on the PK of BI 695501.~Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 40 mg/0.4 mL (T) | Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1518.311 Microgram * hours / milliliter | Geometric Coefficient of Variation 44.69 |
| BI 695501 40 mg/0.8 mL (R) | Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1440.860 Microgram * hours / milliliter | Geometric Coefficient of Variation 44.69 |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of covariance (ANCOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANCOVA model. This model included effects accounting for the following sources of variation: 'treatment', 'location of trial medication injection' and 'baseline body weight' (continuous).90% CI: [95.06, 116.81]
Primary
Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 to 1344 Hours After Dose Administration (AUC0-1344)
Area under the concentration-time curve of BI 695501 in plasma over the time interval from 0 to 1344 hours after dose administration (AUC0-1344). The presented means are adjusted based on analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment, location of trial medication injection and baseline body weight.
Time frame: BI 695501 was measured within 1 hour before and 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration.
Population: Pharmacokinetic analysis set (PKS): The pharmacokinetic set consisted of all randomized subjects who received the single dose of trial medication, and had at least one evaluable primary pharmacokinetics (PK) parameter, and were without important protocol deviations or violations thought to have a relevant impact on the PK of BI 695501.~Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 40 mg/0.4 mL (T) | Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 to 1344 Hours After Dose Administration (AUC0-1344) | 1415.103 Microgram * hours / milliliter | Geometric Coefficient of Variation 37.6 |
| BI 695501 40 mg/0.8 mL (R) | Area Under the Concentration-time Curve of BI 695501 in Plasma Over the Time Interval From 0 to 1344 Hours After Dose Administration (AUC0-1344) | 1389.021 Microgram * hours / milliliter | Geometric Coefficient of Variation 37.6 |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of covariance (ANCOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANCOVA model. This model included effects accounting for the following sources of variation: 'treatment', 'location of trial medication injection' and 'baseline body weight' (continuous).90% CI: [93.31, 111.23]
Primary
Maximum Measured Concentration of BI 695501 in Plasma (Cmax)
Maximum measured concentration of BI 695501 in plasma (Cmax). The presented means are adjusted based on analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment, location of trial medication injection and baseline body weight.
Time frame: BI 695501 was measured within 1 hour before and 4, 12, 24, 48, 72, 96, 120, 144, 168, 216, 336, 504, 672, 840, 1008 and 1344 hours after drug administration.
Population: Pharmacokinetic analysis set (PKS): The pharmacokinetic set consisted of all randomized subjects who received the single dose of trial medication, and had at least one evaluable primary pharmacokinetics (PK) parameter, and were without important protocol deviations or violations thought to have a relevant impact on the PK of BI 695501.~Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 695501 40 mg/0.4 mL (T) | Maximum Measured Concentration of BI 695501 in Plasma (Cmax) | 2.811 Microgram / milliliter | Geometric Coefficient of Variation 34.215 |
| BI 695501 40 mg/0.8 mL (R) | Maximum Measured Concentration of BI 695501 in Plasma (Cmax) | 3.079 Microgram / milliliter | Geometric Coefficient of Variation 34.215 |
Comparison: The statistical model used for the analysis of the primary endpoints was an analysis of covariance (ANCOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANCOVA model. This model included effects accounting for the following sources of variation: 'treatment', 'location of trial medication injection' and 'baseline body weight' (continuous).90% CI: [84.38, 98.76]