Healthy
Conditions
Brief summary
To investigate the effect of the P-gp inducer rifampicin on the pharmacokinetic parameters of nintedanib
Interventions
DRUGNintedanib
single dose administration
DRUGRifampicin
single dose once daily for 7 days
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
1\. Healthy male subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib | AUC0-∞ represents the Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Maximum Measured Concentration (Cmax) | 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib | Cmax represents the maximum concentration of nintedanib in plasma. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib | AUC0-tz represents the area under the plasma concentration-time curve of nintedanib from 0 to the last quantifiable analyte plasma concentration. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study This was an open-label, two-period, fixed-sequence trial. During the first period 150 mg of nintedanib was administered orally in form of a soft gelatine capsule. In the second period, a single dose of 600 mg of rifampicin was administered orally via film-coated tablet every day for a week, then a single dose of nintedanib was administered. The administrations of nintedanib were separated by a washout period of at least 14 days. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Washout Period of at Least 14 Days | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 26 | 2 / 26 | 25 / 25 | 4 / 25 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 0 / 25 | 0 / 25 |
Outcome results
Primary
Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞ represents the Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib
Population: TS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | 183 ng*h/mL | Geometric Coefficient of Variation 36.1 |
| Nintedanib + Rifampicin | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | 89.4 ng*h/mL | Geometric Coefficient of Variation 36.8 |
p-value: 190% CI: [47.155, 53.275]ANOVA
Primary
Maximum Measured Concentration (Cmax)
Cmax represents the maximum concentration of nintedanib in plasma. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib
Population: TS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Maximum Measured Concentration (Cmax) | 22.1 ng/mL | Geometric Coefficient of Variation 51.8 |
| Nintedanib + Rifampicin | Maximum Measured Concentration (Cmax) | 12.8 ng/mL | Geometric Coefficient of Variation 43.4 |
p-value: 190% CI: [53.829, 66.348]ANOVA
Secondary
Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz)
AUC0-tz represents the area under the plasma concentration-time curve of nintedanib from 0 to the last quantifiable analyte plasma concentration. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib
Population: TS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | 173 ng*h/mL | Geometric Coefficient of Variation 36.9 |
| Nintedanib + Rifampicin | Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | 84.1 ng*h/mL | Geometric Coefficient of Variation 38.1 |
p-value: 190% CI: [46.886, 53.286]ANOVA