Healthy
Conditions
Brief summary
To investigate the effect of steady-state itraconazole on the pharmacokinetics of steady-state of faldaprevir and the effect of steady-state of faldaprevir on the single-dose pharmacokinetics of atorvastatin as well as the effect of steady-state of faldaprevir on the single-dose pharmacokinetics of rosuvastatin
Interventions
DRUGItraconazole
twice daily
DRUGAtorvastatin
single dose
DRUGFaldaprevir
once daily
DRUGRosuvastatin
single dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
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 conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Rosuvastatin | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods | Maximum measured concentration of the analyte in plasma of rosuvastatin (Cmax). Outcome measure for the statins part of this trial, treatment sequence E\_F. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Cmax,ss (Itraconazole Part) | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00 h after administration of faldaprevir on Day 1 of both periods. | Maximum measured concentration of the analyte in plasma at steady state over the dosing interval (Cmax,ss) of faldaprevir. Outcome measure for the itraconazole part (Treatment sequence A\_B) of this trial. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| AUC0-∞ of Atorvastatin (Statins Part) | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of atorvastatin after single dose administration. Outcome measure for the statins part of this trial, treatment sequence C\_D. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Cmax of Atorvastatin (Statins Part) | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods | Maximum measured concentration of the analyte in plasma of atorvastatin (Cmax). Outcome measure for the statins part of this trial, treatment sequence C\_D. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| AUC0-∞ of Rosuvastatin (Statins Part) | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of rosuvastatin after single dose administration of rosuvastatin. Outcome measure for the statins part of this trial, treatment sequence E\_F. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| AUCτ,ss (Itraconazole Part) | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00 h (hours) after administration of faldaprevir on Day 1 of both periods | Area under the concentration-time curve of the analyte in plasma at steady state over the dosing interval τ (AUCτ,ss) of faldaprevir. Outcome measure for the itraconazole part (treatment sequence A\_B) of this trial. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,ss of Faldaprevir (Statins Part) | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin/atorvastatin on Day 1 of the second periods of each treatment sequence. | Maximum measured concentration of the analyte in plasma at steady state over the dosing interval (Cmax,ss) of faldaprevir. Outcome measure for the statins part of this trial, treatment sequences C\_D and E\_F. |
| AUC0-tz of Atorvastatin | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods | Area under the plasma concentration-time curve of the analyte over the time interval from 0 to the time tz of the last measurable concentration (AUC0-tz) of atorvastatin. Outcome measure for the statins part of this trial, treatment sequence C\_D. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| AUC0-tz of Rosuvastatin | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods | Area under the plasma concentration-time curve of the analyte over the time interval from 0 to the time tz of the last measurable concentration (AUC0-tz) of rosuvastatin. Outcome measure for the statins part of this trial, treatment sequence E\_F. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| AUCτ,ss of Faldaprevir (Statins Part) | -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin/atorvastatin on Day 1 of the second periods of each treatment sequence. | Area under the concentration-time curve of the analyte in plasma at steady state over the dosing interval τ (AUCτ,ss) of faldaprevir. Outcome measure for the statins part of this trial, treatment sequences C\_D and E\_F. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence A_B (Itraconazole Part) The itraconazole part (interaction of steady state faldaprevir with itraconazole) of this trial was done open-label with a fixed-sequence, 2-period design; performed independently from the statins part.
Treatment A: Faldaprevir (120 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 1 (6 days in total).
Treatment B: Faldaprevir (120 mg) was given once daily from Day -3 to Day 1 (4 days). In addition, itraconazole (200 mg) was given twice daily on Day -3 and once daily from Day -2 to Day 1 (4 days in total).
Treatment A directly preceded treatment B, without an intermittent washout period.
Oral administration with 240 mL water. | 18 |
| Treatment Sequence C_D (Statins Part) The statins part (interaction of multiple dose faldaprevir with either atorvastatin or rosuvastatin) was done open-label with a fixed-sequence, 2-period design; performed independently from the itraconazole part.
Treatment C: Atorvastatin (10 mg) was given as a single dose on Day 1.
Treatment D: Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, atorvastatin (10 mg) was given as a single dose on Day 1.
Treatment C preceded treatment D.
Oral administration with 240 mL water. | 16 |
| Treatment Sequence E_F (Statins Part) The statins part (interaction of multiple dose faldaprevir with either atorvastatin or rosuvastatin) was done open-label with a fixed-sequence, 2-period design; performed independently from the itraconazole part.
Treatment E: Rosuvastatin (10 mg) was given as a single dose on Day 1.
Treatment F: Faldaprevir (240 mg) was given twice daily on Day -5 and once daily from Day -4 to Day 2 (7 days in total). In addition, rosuvastatin (10 mg) was given as a single dose on Day 1.
Treatment E preceded treatment F.
Oral administration with 240 mL water. | 17 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Sequence A_B (Itraconazole Part) | Treatment Sequence C_D (Statins Part) | Treatment Sequence E_F (Statins Part) | Total |
|---|---|---|---|---|
| Age, Continuous | 39.8 years STANDARD_DEVIATION 6.8 | 40.0 years STANDARD_DEVIATION 8.3 | 38.1 years STANDARD_DEVIATION 7.4 | 39.3 years STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 7 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 18 | 3 / 17 | 5 / 16 | 4 / 17 | 23 / 32 | 8 / 15 | 9 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 16 | 0 / 17 | 0 / 32 | 0 / 15 | 0 / 17 |
Outcome results
Primary
AUC0-∞ of Atorvastatin (Statins Part)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of atorvastatin after single dose administration. Outcome measure for the statins part of this trial, treatment sequence C\_D. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods.
Population: PK set of the statins part and assigned to atorvastatin (treatment sequence C\_D).~Pharmacokinetic set (PK set): all treated subjects of the statins part 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 | AUC0-∞ of Atorvastatin (Statins Part) | 13.7 ng*h/mL | Geometric Coefficient of Variation 51.5 |
| Faldaprevir+Itraconazole | AUC0-∞ of Atorvastatin (Statins Part) | 129.0 ng*h/mL | Geometric Coefficient of Variation 43.7 |
Comparison: Relative bioavailability comparison atorvastatin+faldaprevir : atorvastatin.90% CI: [797.61, 1123.07]ANOVA
Primary
AUC0-∞ of Rosuvastatin (Statins Part)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of rosuvastatin after single dose administration of rosuvastatin. Outcome measure for the statins part of this trial, treatment sequence E\_F. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods
Population: PK set of the statins part and assigned to rosuvastatin (treatment sequence E\_F).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | AUC0-∞ of Rosuvastatin (Statins Part) | 24.9 ng*h/mL | Geometric Coefficient of Variation 49.3 |
| Faldaprevir+Itraconazole | AUC0-∞ of Rosuvastatin (Statins Part) | 365.0 ng*h/mL | Geometric Coefficient of Variation 28.6 |
Comparison: Relative bioavailability comparison rosuvastatin+faldaprevir : rosuvastatin.90% CI: [1277.62, 1682.95]ANOVA
Primary
AUCτ,ss (Itraconazole Part)
Area under the concentration-time curve of the analyte in plasma at steady state over the dosing interval τ (AUCτ,ss) of faldaprevir. Outcome measure for the itraconazole part (treatment sequence A\_B) of this trial. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00 h (hours) after administration of faldaprevir on Day 1 of both periods
Population: pharmacokinetic (PK) set of the itraconazole part of this trial. The PK set included all treated subjects of the itraconazole part that provided at least 1 observation for at least 1 primary endpoint without important protocal violations with respect to the statistical evaluation of the PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | AUCτ,ss (Itraconazole Part) | 29900 ng*h/mL | Geometric Coefficient of Variation 62.8 |
| Faldaprevir+Itraconazole | AUCτ,ss (Itraconazole Part) | 59500 ng*h/mL | Geometric Coefficient of Variation 53.8 |
Comparison: Relative bioavailability comparison faldaprevir+itraconazole : faldaprevir90% CI: [182.43, 216.09]ANOVA
Primary
Cmax of Atorvastatin (Statins Part)
Maximum measured concentration of the analyte in plasma of atorvastatin (Cmax). Outcome measure for the statins part of this trial, treatment sequence C\_D. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods
Population: PK set of the statins part and assigned to atorvastatin (treatment sequence C\_D).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | Cmax of Atorvastatin (Statins Part) | 0.94 ng/mL | Geometric Coefficient of Variation 35.2 |
| Faldaprevir+Itraconazole | Cmax of Atorvastatin (Statins Part) | 31.10 ng/mL | Geometric Coefficient of Variation 52.5 |
Comparison: Relative bioavailability comparison atorvastatin+faldaprevir : atorvastatin.90% CI: [2961.95, 3840.47]ANOVA
Primary
Cmax of Rosuvastatin
Maximum measured concentration of the analyte in plasma of rosuvastatin (Cmax). Outcome measure for the statins part of this trial, treatment sequence E\_F. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods
Population: PK set of the statins part and assigned to rosuvastatin (treatment sequence E\_F).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | Cmax of Rosuvastatin | 2.73 ng/mL | Geometric Coefficient of Variation 53 |
| Faldaprevir+Itraconazole | Cmax of Rosuvastatin | 89.6 ng/mL | Geometric Coefficient of Variation 33.2 |
Comparison: Relative bioavailability comparison rosuvastatin+faldaprevir : rosuvastatin.90% CI: [2782.04, 3887.63]ANOVA
Primary
Cmax,ss (Itraconazole Part)
Maximum measured concentration of the analyte in plasma at steady state over the dosing interval (Cmax,ss) of faldaprevir. Outcome measure for the itraconazole part (Treatment sequence A\_B) of this trial. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00 h after administration of faldaprevir on Day 1 of both periods.
Population: PK set of the itraconazole part of this trial.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | Cmax,ss (Itraconazole Part) | 2780 ng/mL | Geometric Coefficient of Variation 61 |
| Faldaprevir+Itraconazole | Cmax,ss (Itraconazole Part) | 5030 ng/mL | Geometric Coefficient of Variation 49.1 |
Comparison: Relative bioavailability comparison faldaprevir+itraconazole : faldaprevir.90% CI: [165.68, 196.93]ANOVA
Secondary
AUC0-tz of Atorvastatin
Area under the plasma concentration-time curve of the analyte over the time interval from 0 to the time tz of the last measurable concentration (AUC0-tz) of atorvastatin. Outcome measure for the statins part of this trial, treatment sequence C\_D. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of atorvastatin on Day 1 of both periods
Population: PK set of the statins part and assigned to atorvastatin (treatment sequence C\_D).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | AUC0-tz of Atorvastatin | 9.5 ng*h/mL | Geometric Coefficient of Variation 40.2 |
| Faldaprevir+Itraconazole | AUC0-tz of Atorvastatin | 129.6 ng*h/mL | Geometric Coefficient of Variation 44.9 |
Comparison: Relative bioavailability comparison atorvastatin+faldaprevir : atorvastatin.90% CI: [1224.32, 1508.29]ANOVA
Secondary
AUC0-tz of Rosuvastatin
Area under the plasma concentration-time curve of the analyte over the time interval from 0 to the time tz of the last measurable concentration (AUC0-tz) of rosuvastatin. Outcome measure for the statins part of this trial, treatment sequence E\_F. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin on Day 1 of both periods
Population: PK set of the statins part and assigned to rosuvastatin (treatment sequence E\_F).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | AUC0-tz of Rosuvastatin | 21.5 ng*h/mL | Geometric Coefficient of Variation 48 |
| Faldaprevir+Itraconazole | AUC0-tz of Rosuvastatin | 361.0 ng*h/mL | Geometric Coefficient of Variation 28.8 |
Comparison: Relative bioavailability comparison rosuvastatin+faldaprevir : rosuvastatin.90% CI: [1468.52, 1917.89]ANOVA
Secondary
AUCτ,ss of Faldaprevir (Statins Part)
Area under the concentration-time curve of the analyte in plasma at steady state over the dosing interval τ (AUCτ,ss) of faldaprevir. Outcome measure for the statins part of this trial, treatment sequences C\_D and E\_F.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin/atorvastatin on Day 1 of the second periods of each treatment sequence.
Population: PK set of the statins part.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | AUCτ,ss of Faldaprevir (Statins Part) | 145000 ng*h/mL | Geometric Coefficient of Variation 34.3 |
| Faldaprevir+Itraconazole | AUCτ,ss of Faldaprevir (Statins Part) | 136000 ng*h/mL | Geometric Coefficient of Variation 43.9 |
Secondary
Cmax,ss of Faldaprevir (Statins Part)
Maximum measured concentration of the analyte in plasma at steady state over the dosing interval (Cmax,ss) of faldaprevir. Outcome measure for the statins part of this trial, treatment sequences C\_D and E\_F.
Time frame: -1:30, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 48:00, 60:00 h after administration of rosuvastatin/atorvastatin on Day 1 of the second periods of each treatment sequence.
Population: PK set of the statins part.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Faldaprevir | Cmax,ss of Faldaprevir (Statins Part) | 12900 ng/mL | Geometric Coefficient of Variation 27.8 |
| Faldaprevir+Itraconazole | Cmax,ss of Faldaprevir (Statins Part) | 12200 ng/mL | Geometric Coefficient of Variation 36.8 |