Healthy
Conditions
Brief summary
The objective of the current study is to investigate the effect of the P-gp inducer rifampicin on the pharmacokinetics (PK) of afatinib in healthy male volunteers
Interventions
DRUGAfatinib
single dose
DRUGRifampicin
multiple doses
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy male volunteers
Exclusion criteria
Any relevant deviations from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve From 0 to Infinity Hours (AUC0-∞) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | AUC0-∞ represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. |
| Area Under Curve From 0 to tz (AUC0-tz) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | AUC0-tz represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. |
| Maximum Concentration (Cmax) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | Cmax represents the maximum concentration of the analyte in plasma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of the AUCtz-∞ Obtained by Extrapolation (%AUCtz-∞) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | %AUCtz-∞ represents the percentage of the AUCtz-∞ obtained by extrapolation |
| Mean Residence Time of Afatinib in the Body After Oral Administration (MRTpo) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | MRTpo represents the mean residence time of the analyte in the body after oral administration |
| Time From Dosing to the Maximum Concentration of Afatinib in Plasma (Tmax) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | tmax represents the time from dosing to the maximum concentration of the analyte in plasma |
| Apparent Volume of Distribution During the Terminal Phase lambda_z Following an Extravascular Dose (V_z/F) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | V\_z/F represents the apparent volume of distribution during the terminal phase λz following an extravascular dose |
| Apparent Clearance of Afatinib in the Plasma After Extravascular Administration (CL/F) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | CL/F represents the apparent clearance of the analyte in the plasma after extravascular administration |
| Terminal Half-life of Afatinib in Plasma (t1/2) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | t1/2 represents the terminal half-life of the analyte in plasma |
| Area Under Curve From 0 to 24 h (AUC0-24) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | AUC0-24 represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (h) |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study This was a open-label, two period, fixed sequence trial clinical phase I trial in healthy male volunteers. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Rifa+Afatinib | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 22 | 4 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Area Under Curve From 0 to Infinity Hours (AUC0-∞)
AUC0-∞ represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Area Under Curve From 0 to Infinity Hours (AUC0-∞) | 912 ng*h/mL | Geometric Coefficient of Variation 38.3 |
| Afatinib + Rifa | Area Under Curve From 0 to Infinity Hours (AUC0-∞) | 610 ng*h/mL | Geometric Coefficient of Variation 32.1 |
90% CI: [60.815, 72.057]ANOVA
Primary
Area Under Curve From 0 to tz (AUC0-tz)
AUC0-tz represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration.
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Area Under Curve From 0 to tz (AUC0-tz) | 860 ng*h/mL | Geometric Coefficient of Variation 39.8 |
| Afatinib + Rifa | Area Under Curve From 0 to tz (AUC0-tz) | 575 ng*h/mL | Geometric Coefficient of Variation 32.3 |
90% CI: [60.656, 72.213]ANOVA
Primary
Maximum Concentration (Cmax)
Cmax represents the maximum concentration of the analyte in plasma.
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Maximum Concentration (Cmax) | 38.3 ng/mL | Geometric Coefficient of Variation 38.4 |
| Afatinib + Rifa | Maximum Concentration (Cmax) | 30.0 ng/mL | Geometric Coefficient of Variation 34.1 |
90% CI: [72.363, 84.968]ANOVA
Secondary
Apparent Clearance of Afatinib in the Plasma After Extravascular Administration (CL/F)
CL/F represents the apparent clearance of the analyte in the plasma after extravascular administration
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Apparent Clearance of Afatinib in the Plasma After Extravascular Administration (CL/F) | 731 mL/min | Geometric Coefficient of Variation 38.3 |
| Afatinib + Rifa | Apparent Clearance of Afatinib in the Plasma After Extravascular Administration (CL/F) | 1090 mL/min | Geometric Coefficient of Variation 32.1 |
Secondary
Apparent Volume of Distribution During the Terminal Phase lambda_z Following an Extravascular Dose (V_z/F)
V\_z/F represents the apparent volume of distribution during the terminal phase λz following an extravascular dose
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Apparent Volume of Distribution During the Terminal Phase lambda_z Following an Extravascular Dose (V_z/F) | 2080 Litres | Geometric Coefficient of Variation 53.2 |
| Afatinib + Rifa | Apparent Volume of Distribution During the Terminal Phase lambda_z Following an Extravascular Dose (V_z/F) | 3410 Litres | Geometric Coefficient of Variation 34.7 |
Secondary
Area Under Curve From 0 to 24 h (AUC0-24)
AUC0-24 represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (h)
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Area Under Curve From 0 to 24 h (AUC0-24) | 491 ng*h/mL | Geometric Coefficient of Variation 41.4 |
| Afatinib + Rifa | Area Under Curve From 0 to 24 h (AUC0-24) | 353 ng*h/mL | Geometric Coefficient of Variation 35 |
Secondary
Mean Residence Time of Afatinib in the Body After Oral Administration (MRTpo)
MRTpo represents the mean residence time of the analyte in the body after oral administration
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Mean Residence Time of Afatinib in the Body After Oral Administration (MRTpo) | 36.9 hours | Geometric Coefficient of Variation 14.3 |
| Afatinib + Rifa | Mean Residence Time of Afatinib in the Body After Oral Administration (MRTpo) | 35.1 hours | Geometric Coefficient of Variation 14 |
Secondary
Percentage of the AUCtz-∞ Obtained by Extrapolation (%AUCtz-∞)
%AUCtz-∞ represents the percentage of the AUCtz-∞ obtained by extrapolation
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Percentage of the AUCtz-∞ Obtained by Extrapolation (%AUCtz-∞) | 5.25 percentage of AUCtz-∞ | Geometric Coefficient of Variation 44.8 |
| Afatinib + Rifa | Percentage of the AUCtz-∞ Obtained by Extrapolation (%AUCtz-∞) | 5.48 percentage of AUCtz-∞ | Geometric Coefficient of Variation 31.1 |
Secondary
Terminal Half-life of Afatinib in Plasma (t1/2)
t1/2 represents the terminal half-life of the analyte in plasma
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Terminal Half-life of Afatinib in Plasma (t1/2) | 32.8 hours | Geometric Coefficient of Variation 18.4 |
| Afatinib + Rifa | Terminal Half-life of Afatinib in Plasma (t1/2) | 36.0 hours | Geometric Coefficient of Variation 15.1 |
Secondary
Time From Dosing to the Maximum Concentration of Afatinib in Plasma (Tmax)
tmax represents the time from dosing to the maximum concentration of the analyte in plasma
Time frame: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose
Population: PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Afatinib | Time From Dosing to the Maximum Concentration of Afatinib in Plasma (Tmax) | 6.00 hours |
| Afatinib + Rifa | Time From Dosing to the Maximum Concentration of Afatinib in Plasma (Tmax) | 6.00 hours |