Healthy
Conditions
Brief summary
The objective of the current study is to investigate the relative bioavailability of two different doses of BI 201335, administered as soft gelatine capsule in comparison to the equivalent doses of three different oral solution per dose of BI 201335.
Interventions
DRUGBI 201335 (Reference)
soft gelatine capsule, oral administration
DRUGBI 201335 (Test)
oral solution 3
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Healthy male and female subjects
Exclusion criteria
Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-∞ | -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h (hours) after administration of faldaprevir on Day 1. | Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 extrapolated to infinity. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Cmax | -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1. | Maximum measured concentration of the analyte (faldaprevir) in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| AUC0-tz | -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1. | Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 to the time of the last quantifiable data point. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 40mg Faldaprevir: Sequence Group ADBC 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D).
The order of treatment administration in this sequence group is ADBC with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 5 |
| 40mg Faldaprevir: Sequence Group BACD 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D).
The order of treatment administration in this sequence group is BACD with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 5 |
| 40mg Faldaprevir: Sequence Group CBDA 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D).
The order of treatment administration in this sequence group is CBDA with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 5 |
| 40mg Faldaprevir: Sequence Group DCAB 40 mg group: The reference treatment was a single 40 mg dose of faldaprevir soft gelatine capsule (treatment A) and the test treatments were single 40 mg doses of 3 different faldaprevir oral solutions (treatments B, C, and D).
The order of treatment administration in this sequence group is DCAB with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 5 |
| 120mg Faldaprevir: Sequence Group EHFG 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H).
The order of treatment administration in this sequence group is EHFG with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 10 |
| 120mg Faldaprevir: Sequence Group FEGH 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H).
The order of treatment administration in this sequence group is FEGH with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 8 |
| 120mg Faldaprevir: Sequence Group GFHE 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H).
The order of treatment administration in this sequence group is GFHE with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 9 |
| 120mg Faldaprevir: Sequence Group HGEF 120 mg group: The reference treatment was a single 120 mg dose (consisting of three 40 mg faldaprevir soft gelatine capsules, treatment E) and the test treatments were single 120 mg doses of 3 different faldaprevir oral solutions (treatments F, G, and H).
The order of treatment administration in this sequence group is HGEF with washout phases of at least 14 days between drug administrations.
Oral administration (under fed conditions, i.e. following a high-fat breakfast). | 9 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 40mg Faldaprevir: Sequence Group ADBC | 40mg Faldaprevir: Sequence Group BACD | 40mg Faldaprevir: Sequence Group CBDA | 40mg Faldaprevir: Sequence Group DCAB | 120mg Faldaprevir: Sequence Group EHFG | 120mg Faldaprevir: Sequence Group FEGH | 120mg Faldaprevir: Sequence Group GFHE | 120mg Faldaprevir: Sequence Group HGEF | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 41.2 years STANDARD_DEVIATION 5.3 | 39.8 years STANDARD_DEVIATION 5.1 | 38.0 years STANDARD_DEVIATION 10.2 | 44.4 years STANDARD_DEVIATION 4.2 | 33.9 years STANDARD_DEVIATION 9.7 | 38.6 years STANDARD_DEVIATION 9.6 | 39.4 years STANDARD_DEVIATION 8.1 | 34.9 years STANDARD_DEVIATION 9.5 | 38.1 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 5 Participants | 4 Participants | 7 Participants | 3 Participants | 28 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 5 Participants | 4 Participants | 2 Participants | 6 Participants | 28 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 | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 19 | 2 / 20 | 8 / 20 | 6 / 19 | 6 / 35 | 5 / 36 | 7 / 36 | 8 / 35 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 | 0 / 20 | 0 / 19 | 0 / 35 | 0 / 36 | 0 / 36 | 0 / 35 |
Outcome results
Primary
AUC0-∞
Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 extrapolated to infinity. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h (hours) after administration of faldaprevir on Day 1.
Population: Pharmacokinetic analysis set (PK set) includes all subjects who provided evaluable data for at least 1 evaluable observation for a PK endpoint in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 40mg Faldaprevir: Treatment A | AUC0-∞ | 3960 ng*h/mL | Geometric Coefficient of Variation 32.3 |
| 40mg Faldaprevir: Treatment B | AUC0-∞ | 3400 ng*h/mL | Geometric Coefficient of Variation 28.5 |
| 40mg Faldaprevir: Treatment C | AUC0-∞ | 3350 ng*h/mL | Geometric Coefficient of Variation 28.4 |
| 40mg Faldaprevir: Treatment D | AUC0-∞ | 3420 ng*h/mL | Geometric Coefficient of Variation 30.4 |
| 120mg Faldaprevir: Treatment E | AUC0-∞ | 15000 ng*h/mL | Geometric Coefficient of Variation 34.5 |
| 120mg Faldaprevir: Treatment F | AUC0-∞ | 13900 ng*h/mL | Geometric Coefficient of Variation 38.8 |
| 120mg Faldaprevir: Treatment G | AUC0-∞ | 14500 ng*h/mL | Geometric Coefficient of Variation 38.3 |
| 120mg Faldaprevir: Treatment H | AUC0-∞ | 14100 ng*h/mL | Geometric Coefficient of Variation 36 |
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment B : treatment A).90% CI: [73.69, 92.54]ANOVA
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment C : treatment A).90% CI: [73.65, 94.3]ANOVA
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment D : treatment A).90% CI: [74.69, 94.28]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment F : treatment E).90% CI: [88.94, 97.04]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment G : treatment E).90% CI: [91.55, 101.43]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment H : treatment E).90% CI: [89.88, 99.24]ANOVA
Primary
AUC0-tz
Area under the concentration-time curve of the analyte (faldaprevir) in plasma over the time interval from 0 to the time of the last quantifiable data point. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1.
Population: PK set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 40mg Faldaprevir: Treatment A | AUC0-tz | 3020 ng*h/mL | Geometric Coefficient of Variation 29.4 |
| 40mg Faldaprevir: Treatment B | AUC0-tz | 2600 ng*h/mL | Geometric Coefficient of Variation 32.9 |
| 40mg Faldaprevir: Treatment C | AUC0-tz | 2520 ng*h/mL | Geometric Coefficient of Variation 38.3 |
| 40mg Faldaprevir: Treatment D | AUC0-tz | 2550 ng*h/mL | Geometric Coefficient of Variation 34.3 |
| 120mg Faldaprevir: Treatment E | AUC0-tz | 14200 ng*h/mL | Geometric Coefficient of Variation 35.2 |
| 120mg Faldaprevir: Treatment F | AUC0-tz | 12900 ng*h/mL | Geometric Coefficient of Variation 39.4 |
| 120mg Faldaprevir: Treatment G | AUC0-tz | 13400 ng*h/mL | Geometric Coefficient of Variation 38 |
| 120mg Faldaprevir: Treatment H | AUC0-tz | 13100 ng*h/mL | Geometric Coefficient of Variation 37 |
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment B : treatment A).90% CI: [75.98, 88.55]ANOVA
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment C : treatment A).90% CI: [74.58, 87.83]ANOVA
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment D : treatment A).90% CI: [74.84, 84.67]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment F : treatment E).90% CI: [87.53, 95.84]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment G : treatment E).90% CI: [89.76, 99.24]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment H : treatment E).90% CI: [88.42, 97.63]ANOVA
Primary
Cmax
Maximum measured concentration of the analyte (faldaprevir) in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: -1:00, 1:00, 2:00, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 9:00, 10:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00 h after administration of faldaprevir on Day 1.
Population: PK set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 40mg Faldaprevir: Treatment A | Cmax | 86.4 ng/mL | Geometric Coefficient of Variation 36 |
| 40mg Faldaprevir: Treatment B | Cmax | 65.4 ng/mL | Geometric Coefficient of Variation 39 |
| 40mg Faldaprevir: Treatment C | Cmax | 64.0 ng/mL | Geometric Coefficient of Variation 40.4 |
| 40mg Faldaprevir: Treatment D | Cmax | 69.7 ng/mL | Geometric Coefficient of Variation 28.1 |
| 120mg Faldaprevir: Treatment E | Cmax | 625.0 ng/mL | Geometric Coefficient of Variation 47.3 |
| 120mg Faldaprevir: Treatment F | Cmax | 481.0 ng/mL | Geometric Coefficient of Variation 47.1 |
| 120mg Faldaprevir: Treatment G | Cmax | 488.0 ng/mL | Geometric Coefficient of Variation 52.1 |
| 120mg Faldaprevir: Treatment H | Cmax | 485.0 ng/mL | Geometric Coefficient of Variation 48.4 |
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment B : treatment A).90% CI: [65.44, 83.83]ANOVA
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment C : treatment A).90% CI: [63.33, 84.68]ANOVA
Comparison: relative bioavailability comparison of 40 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment D : treatment A).90% CI: [68.94, 89.99]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment F : treatment E).90% CI: [71.42, 85.84]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment G : treatment E).90% CI: [69.54, 88.46]ANOVA
Comparison: relative bioavailability comparison of 120 mg faldaprevir soft gelatine capsules compared with the equivalent dose of an oral solution.~(treatment H : treatment E).90% CI: [69.35, 87.94]ANOVA