Hepatitis C
Conditions
Brief summary
The objective is to investigate the bioequivalence of 2 dose strengths of 40 mg and 120 mg BI 201335 NA soft gelatine capsules.
Interventions
DRUGBI 201335 NA 120 mg capsule
1capsule of BI 201335 NA 120 mg capsule
DRUGBI 201335 NA 40 mg capsule
3 capsules of BI 201335 NA 40 mg capsule
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male volunteers without any clinical significant findings and complications 2. Age: 20 - 45 years 3. BMI: 18.5 - 25.0 kg/m2 4. Signed informed consent
Exclusion criteria
1. Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance. 2. Any evidence of a clinically relevant concomitant disease according to investigator's clinical judgement. 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders. 4. History of jaundice 5. Surgery of the gastrointestinal tract (except appendectomy). 6. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders. 7. History of relevant orthostatic hypotension, fainting spells or blackouts. 8. Chronic or relevant acute infections. 9. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) according to investigator's clinical judgement. 10. Intake of drugs with a long half-life (\>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial 11. Use of drugs which might reasonably influence the results (pharmacokinetic) of the trial within at least 10 days prior to administration or during the trial. 12. Participation in another trial with an investigational drug within two months prior to administration or during the trial. 13. Smoking (\>10 cigarettes or \>3 cigars or \>3 pipes/day). 14. Inability to refrain from smoking during the trial. 15. Alcohol abuse (more than 60 g/day: e.g., 3 middle-sized bottles of beer, 3 gous \[equivalent to 540 mL\] of sake). 16. Drug abuse. 17. Blood donation (more than 100 mL within four weeks prior to administration). 18. Excessive physical activities (within one week prior to administration). 19. Any laboratory value outside the reference range that is of clinical relevance according to investigator's clinical judgement. 20. Any history of relevant liver diseases (for instance, disturbances of liver function, Dubin-Johnson syndrome, Rotor syndrome, or previous liver tumours).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of the Analyte From Time 0 to the Last Quantifiable Data Point (AUC0-tz) | 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration | Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 to the time of the last quantifiable data point. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation. |
| Maximum Measured Concentration (Cmax) | 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration | Maximum measured concentration of faldaprevir in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Rate Constant (λz) | 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration | Terminal rate constant of the analyte in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation. |
| Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration | Area under the concentration-time curve of faldaprevir in plasma over the time interval from 0 extrapolated to infinity. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation. |
| Mean Residence Time (MRTpo) | 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration | Mean residence time of the analyte in the body after oral administration. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation. |
| Terminal Half-life (t1/2) | 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration | Terminal half-life of faldaprevir in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation. |
| Time From Dosing to the Maximum Measured Concentration (Tmax) | 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration | Time from dosing to the maximum measured concentration of the analyte in plasma. Means presented are adjusted means and the standard deviation is actually the intra-individual coefficient of variation. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1 Treatment sequence: Test - Reference - Reference - Test
Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast.
Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast.
Treatments were separated by a washout period of at least 14 days. | 30 |
| Treatment Sequence 2 Treatment sequence: Reference - Test - Test - Reference
Test product: Oral administration of faldaprevir 120 mg (40 mg x 3 soft gelatine capsules) with 150 mL water after an overnight fast.
Reference Product: Oral administration of faldaprevir 120 mg (120 mg x 1 soft gelatine capsule) with 150 mL water after an overnight fast.
Treatments were separated by a washout period of at least 14 days. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 2 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Sequence 1 | Treatment Sequence 2 | Total |
|---|---|---|---|
| Age, Continuous | 28.1 years STANDARD_DEVIATION 5.7 | 30.1 years STANDARD_DEVIATION 5.8 | 29.1 years STANDARD_DEVIATION 5.8 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 30 Participants | 30 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 59 | 8 / 60 |
| serious Total, serious adverse events | 0 / 59 | 0 / 60 |
Outcome results
Primary
Area Under the Curve of the Analyte From Time 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 time of the last quantifiable data point. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.
Time frame: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Product: Faldaprevir 40 mg x 3 Capsules | Area Under the Curve of the Analyte From Time 0 to the Last Quantifiable Data Point (AUC0-tz) | 17297.157 ng·h/mL | Geometric Coefficient of Variation 19.71 |
| Reference Product: Faldaprevir 120 mg x 1 Capsule | Area Under the Curve of the Analyte From Time 0 to the Last Quantifiable Data Point (AUC0-tz) | 17216.514 ng·h/mL | Geometric Coefficient of Variation 23.89 |
90% CI: [95.9, 105.25]
Primary
Maximum Measured Concentration (Cmax)
Maximum measured concentration of faldaprevir in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.
Time frame: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Product: Faldaprevir 40 mg x 3 Capsules | Maximum Measured Concentration (Cmax) | 943.868 ng/mL | Geometric Coefficient of Variation 32.16 |
| Reference Product: Faldaprevir 120 mg x 1 Capsule | Maximum Measured Concentration (Cmax) | 916.480 ng/mL | Geometric Coefficient of Variation 39.22 |
90% CI: [95.57, 110.98]
Secondary
Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of faldaprevir in plasma over the time interval from 0 extrapolated to infinity. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.
Time frame: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Product: Faldaprevir 40 mg x 3 Capsules | Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 18422.006 ng*h/mL | Geometric Coefficient of Variation 19.07 |
| Reference Product: Faldaprevir 120 mg x 1 Capsule | Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 18323.189 ng*h/mL | Geometric Coefficient of Variation 23.18 |
90% CI: [96.1, 105.18]
Secondary
Mean Residence Time (MRTpo)
Mean residence time of the analyte in the body after oral administration. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.
Time frame: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Product: Faldaprevir 40 mg x 3 Capsules | Mean Residence Time (MRTpo) | 29.948 hour | Geometric Coefficient of Variation 9.93 |
| Reference Product: Faldaprevir 120 mg x 1 Capsule | Mean Residence Time (MRTpo) | 29.888 hour | Geometric Coefficient of Variation 9.79 |
90% CI: [98.1, 102.34]
Secondary
Terminal Half-life (t1/2)
Terminal half-life of faldaprevir in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.
Time frame: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Product: Faldaprevir 40 mg x 3 Capsules | Terminal Half-life (t1/2) | 26.204 hours | Geometric Coefficient of Variation 9.91 |
| Reference Product: Faldaprevir 120 mg x 1 Capsule | Terminal Half-life (t1/2) | 26.293 hours | Geometric Coefficient of Variation 6.91 |
90% CI: [97.85, 101.51]
Secondary
Terminal Rate Constant (λz)
Terminal rate constant of the analyte in plasma. Geometric means presented are adjusted means and the coefficient of variation is the intra-individual geometric coefficient of variation.
Time frame: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Product: Faldaprevir 40 mg x 3 Capsules | Terminal Rate Constant (λz) | 0.0265 1/h | Geometric Coefficient of Variation 9.91 |
| Reference Product: Faldaprevir 120 mg x 1 Capsule | Terminal Rate Constant (λz) | 0.0264 1/h | Geometric Coefficient of Variation 6.91 |
90% CI: [98.51, 102.2]
Secondary
Time From Dosing to the Maximum Measured Concentration (Tmax)
Time from dosing to the maximum measured concentration of the analyte in plasma. Means presented are adjusted means and the standard deviation is actually the intra-individual coefficient of variation.
Time frame: 3 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all healthy subjects in the treated set who have evaluable pharmacokinetic variable in the treatment periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product: Faldaprevir 40 mg x 3 Capsules | Time From Dosing to the Maximum Measured Concentration (Tmax) | 4.478 hours | Standard Deviation 25.6 |
| Reference Product: Faldaprevir 120 mg x 1 Capsule | Time From Dosing to the Maximum Measured Concentration (Tmax) | 4.585 hours | Standard Deviation 31.48 |
90% CI: [91.54, 103.78]