Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the effect of food and of gastric pH increase on the relative bioavailability of faldaprevir.
Interventions
DRUGfaldaprevir
medium dose of faldaprevir
DRUGomeprazole
medium dose of omeprazole
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Healthy male and female subjects
Exclusion criteria
1\. Any relevant deviation from healthy condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Faldaprevir: Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration | Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 extrapolated to infinity In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Faldaprevir: Maximum Measured Concentration (Cmax) | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration | Maximum measured concentration of the faldaprevir in plasma In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Faldaprevir: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration | Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 to the last quantifiable drug plasma concentration In 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, 3-way cross over study with three sequences. Faldaprevir administrations in each treatment period were separated by washout period of at least 14 days.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All subjects received all tested treatments in a randomised, open label, 3-way cross over study. The treatments were:
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration (Reference treatment)
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less.
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir.
Drug administrations were separated by a washout period of at least 14 days | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | other reason not defined above | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 34.7 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 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 | 4 / 15 | 4 / 14 | 4 / 14 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 14 | 0 / 15 |
Outcome results
Primary
Faldaprevir: Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)
Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 extrapolated to infinity In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration
Population: Pharmacokinetic (PK) set: Included all treated subjects that provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of the pharmacokinetic endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir in Fasting | Faldaprevir: Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 37900 [ng*h/mL] | Geometric Coefficient of Variation 67.2 |
| Faldaprevir After a High-fat Meal | Faldaprevir: Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 48200 [ng*h/mL] | Geometric Coefficient of Variation 41.7 |
| Faldaprevir and Omeprazole | Faldaprevir: Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 36000 [ng*h/mL] | Geometric Coefficient of Variation 63.4 |
p-value: 0.34290% CI: [102.09, 141.88]ANOVA
p-value: 0.096290% CI: [76.21, 116.76]ANOVA
Primary
Faldaprevir: Maximum Measured Concentration (Cmax)
Maximum measured concentration of the faldaprevir in plasma In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir in Fasting | Faldaprevir: Maximum Measured Concentration (Cmax) | 2030 ng/mL | Geometric Coefficient of Variation 140 |
| Faldaprevir After a High-fat Meal | Faldaprevir: Maximum Measured Concentration (Cmax) | 2600 ng/mL | Geometric Coefficient of Variation 57.5 |
| Faldaprevir and Omeprazole | Faldaprevir: Maximum Measured Concentration (Cmax) | 1920 ng/mL | Geometric Coefficient of Variation 122 |
p-value: 0.399390% CI: [83.19, 169.628]ANOVA
p-value: 0.220490% CI: [65.783, 133.03]ANOVA
Secondary
Faldaprevir: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 to the last quantifiable drug plasma concentration In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir in Fasting | Faldaprevir: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 36300 ng*h/mL | Geometric Coefficient of Variation 70.3 |
| Faldaprevir After a High-fat Meal | Faldaprevir: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 46400 ng*h/mL | Geometric Coefficient of Variation 42.6 |
| Faldaprevir and Omeprazole | Faldaprevir: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 34400 ng*h/mL | Geometric Coefficient of Variation 65.6 |
p-value: 0.376590% CI: [102.32, 143.74]ANOVA
p-value: 0.094690% CI: [76.25, 117.67]ANOVA