Healthy
Conditions
Brief summary
To study the effect of the P-glycoprotein inhibitor ritonavir on the pharmacokinetics (PK) of afatinib depending on the timepoint of ritonavir administration
Interventions
DRUGafatinib
standard therapeutic dose
DRUGritonavir + afatinib
simultaneous intake of ritonavir and afatinib on second treatment day
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1\. healthy male subjects
Exclusion criteria
1\. any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve From 0 to tz (AUC0-tz) | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post | AUC0-tz represents the area under the concentration curve of the analyte in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte. |
| Maximum Concentration (Cmax) | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post | Cmax represents the maximum concentration of the analyte in plasma. |
| Area Under Curve From 0 to ∞ Hours (AUC0-∞) | 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post | AUC0-∞ represents the area under the concentration curve of the analyte in plasma from 0 extrapolated to infinity. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study This is an open-label, randomized, three-way crossover clinical phase I trial in healthy volunteers. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 23 | 7 / 24 | 5 / 22 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 | 0 / 22 |
Outcome results
Primary
Area Under Curve From 0 to ∞ Hours (AUC0-∞)
AUC0-∞ represents the area under the concentration curve of the analyte in plasma from 0 extrapolated to infinity.
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
Population: This subject set includes all evaluable subjects of the treated set who were assigned to the final dose groups and who provide at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Area Under Curve From 0 to ∞ Hours (AUC0-∞) | 426 ng*h/mL | Geometric Coefficient of Variation 22.8 |
| Afatinib + Concomittant Rtv | Area Under Curve From 0 to ∞ Hours (AUC0-∞) | 515 ng*h/mL | Geometric Coefficient of Variation 27.5 |
| Afatinib + Timed Rtv | Area Under Curve From 0 to ∞ Hours (AUC0-∞) | 475 ng*h/mL | Geometric Coefficient of Variation 19.4 |
p-value: 0.070290% CI: [111.712, 125.822]ANOVA
p-value: 0.000590% CI: [104.936, 116.913]ANOVA
p-value: 0.000390% CI: [86.928, 98.341]ANOVA
Primary
Area Under Curve From 0 to tz (AUC0-tz)
AUC0-tz represents the area under the concentration curve of the analyte in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte.
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
Population: This subject set includes all evaluable subjects of the treated set who were assigned to the final dose groups and who provide at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Area Under Curve From 0 to tz (AUC0-tz) | 392 ng*h/mL | Geometric Coefficient of Variation 26.2 |
| Afatinib + Concomittant Rtv | Area Under Curve From 0 to tz (AUC0-tz) | 478 ng*h/mL | Geometric Coefficient of Variation 27.9 |
| Afatinib + Timed Rtv | Area Under Curve From 0 to tz (AUC0-tz) | 438 ng*h/mL | Geometric Coefficient of Variation 20.3 |
p-value: 0.000490% CI: [86.519, 97.614]ANOVA
p-value: 0.100990% CI: [112.239, 126.811]ANOVA
p-value: 0.000990% CI: [103.837, 117.006]ANOVA
Primary
Maximum Concentration (Cmax)
Cmax represents the maximum concentration of the analyte in plasma.
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
Population: This subject set includes all evaluable subjects of the treated set who were assigned to the final dose groups and who provide at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Afatinib | Maximum Concentration (Cmax) | 19.5 ng/mL | Geometric Coefficient of Variation 33.5 |
| Afatinib + Concomittant Rtv | Maximum Concentration (Cmax) | 20.7 ng/mL | Geometric Coefficient of Variation 29.4 |
| Afatinib + Timed Rtv | Maximum Concentration (Cmax) | 20.7 ng/mL | Geometric Coefficient of Variation 24.4 |
p-value: 0.000290% CI: [96.681, 112.002]ANOVA
p-value: 0.001290% CI: [96.425, 114.53]ANOVA
p-value: 090% CI: [93.328, 106.61]ANOVA