Healthy
Conditions
Brief summary
The objective of the current study is to investigate the relative bioavailability of a single dose of nintedanib low or high dose with and without coadministration of ketoconazole at steady state
Interventions
DRUGNintedanib
low or medium dose depending on pilot part
DRUGKetoconazole
oral administration
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 the Curve From 0 Extrapolated to Infinity (AUC0-∞) | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration | 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 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration | 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 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration | AUC0-tz represents the area under the plasma concentration-time curve of nintedanib from time 0 to the last quantifiable nintedanib plasma concentration. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities |
Countries
Germany
Participant flow
Pre-assignment details
This was a randomised, open-label trial with a 2-way cross-over Pilot part, followed by a 2-way cross-over Main part. Subjects participated either in the Pilot part with 2 treatment sequences (A\_B and B\_A) or in the Main part with treatment sequences (C\_D and D\_C) with wash-out period of at least 14 days between each sequence.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study This was a randomised, open-label trial in healthy male subjects with a 2-way cross-over Pilot part, followed by a 2-way cross-over Main part. Subjects participated either in the Pilot part with 2 treatments (A and B) given in 1 of the 2 treatment sequences (A\_B and B\_A) or in the Main part with also 2 treatments (C and D) given in 1 of the 2 treatment sequences (C\_D and D\_C). Nintedanib administrations of the 2 respective treatments (A and B or C and D) were to be separated by a wash-out period of at least 14 days. The Pilot part was separated from the Main part by at least 3 weeks to allow for interim analysis | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | other than stated above | 0 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 35.9 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 34 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 / 34 | 6 / 31 | 6 / 29 |
| serious Total, serious adverse events | 0 / 34 | 0 / 31 | 0 / 29 |
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 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration
Population: The treated set (TS) includes all subjects who were dispensed study medication and were documented to have taken at least one dose of study medication (nintedanib or ketoconazole).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | 38.6 ng*h/mL | Geometric Coefficient of Variation 42.5 |
| Nintedanib + Ketoconazole | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | 61.3 ng*h/mL | Geometric Coefficient of Variation 40.4 |
p-value: 190% CI: [148.245, 173.736]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 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration
Population: TS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Maximum Measured Concentration (Cmax) | 4.19 ng/mL | Geometric Coefficient of Variation 71 |
| Nintedanib + Ketoconazole | Maximum Measured Concentration (Cmax) | 7.13 ng/mL | Geometric Coefficient of Variation 44.4 |
p-value: 190% CI: [157.557, 204.779]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 time 0 to the last quantifiable nintedanib plasma concentration. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities
Time frame: 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration
Population: TS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | 35.7 ng*h/mL | Geometric Coefficient of Variation 47.8 |
| Nintedanib + Ketoconazole | Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | 59.4 ng*h/mL | Geometric Coefficient of Variation 40.8 |
p-value: 190% CI: [155.252, 181.981]ANOVA