HIV Infections
Conditions
Brief summary
The objective of the current study is to investigate the effect of multiple oral daily doses of BI 201335 on the steady-state pharmacokinetics of darunavir co-administered with ritonavir.
Interventions
DRUGDarunavir
400 mg tablet for oral administration
DRUGRitonavir
tablet for oral administration
DRUGBI 201335
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects according to the following criteria: medical history, physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram (ECG), clinical laboratory tests 2. Age 18 to 55 years (incl.) 3. Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.) and weight greater than 50 kg 4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.
Exclusion criteria
1. Any finding of the medical examination (including blood pressure (BP), pulse rate (PR) and ECG) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. History of photosensitivity or recurrent rash. 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) 10. Intake of drugs with a long half-life (more than 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. Participation in another trial with an investigational drug within two months prior to administration or during the trial 12. Smoker (more than 10 cigarettes) 13. Inability to refrain from smoking on trial days 14. Alcohol abuse (more than 30 g/day) 15. Drug abuse 16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial) 17. ALT outside the normal range or any other laboratory value outside the reference range that is of clinical relevance 18. Inability to comply with dietary regimen of trial site 19. The subject is not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions 20. Positive serology tests for Human immunodeficiency virus (HIV) and hepatitis B / C virus 21. Vulnerable subjects (e.g. persons kept in detention)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCτ,ss of Darunavir | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) | area under the concentration-time curve of the analyte in plasma at steadystate over a uniform dosing interval τ of darunavir. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities |
| Cτ,ss of Darunavir | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) | concentration of the analyte in plasma at steady-state after a uniform dosing interval τ=24h of darunavir |
| Cmax,ss of Darunavir | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) | maximum measured concentration of the analyte in plasma at steady-state |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax,ss of Darunavir | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) | time from last dosing to maximum concentration of the analyte in plasma at steady state |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Subjects The study was performed as an open-label, multiple-dose, single-group, fixed-sequence study in 14 healthy volunteers.
Period 1: darunavir 800 mg once daily coadministered with ritonavir 100 mg (DRV/r).
Period 2: faldaprevir together with DRV/r. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 40.4 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 14 | 11 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
AUCτ,ss of Darunavir
area under the concentration-time curve of the analyte in plasma at steadystate over a uniform dosing interval τ of darunavir. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)
Population: Pharmacokinetic (PK) set: all subjects in the treated set who provided at least one observation for at least one primary endpoint without any important protocol violations relevant to the pharmacokinetic evaluation and who did not experience vomiting at or before 2 times median tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Darunavir+Ritonavir | AUCτ,ss of Darunavir | 57200 ng*h/mL | Geometric Coefficient of Variation 29.5 |
| Faldaprevir+Darunavir+Ritonavir | AUCτ,ss of Darunavir | 66000 ng*h/mL | Geometric Coefficient of Variation 39.9 |
Comparison: relative bioavailability comparison (Faldaprevir+DRV/r : DRV/r) of Darunavir90% CI: [101.36, 131.13]ANOVA
Primary
Cmax,ss of Darunavir
maximum measured concentration of the analyte in plasma at steady-state
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Darunavir+Ritonavir | Cmax,ss of Darunavir | 4930 ng/mL | Geometric Coefficient of Variation 23.9 |
| Faldaprevir+Darunavir+Ritonavir | Cmax,ss of Darunavir | 6330 ng/mL | Geometric Coefficient of Variation 26.5 |
Comparison: relative bioavailability comparison (Faldaprevir+DRV/r : DRV/r) of Darunavir90% CI: [115.724, 142.489]ANOVA
Primary
Cτ,ss of Darunavir
concentration of the analyte in plasma at steady-state after a uniform dosing interval τ=24h of darunavir
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Darunavir+Ritonavir | Cτ,ss of Darunavir | 1330 ng/mL | Geometric Coefficient of Variation 49.5 |
| Faldaprevir+Darunavir+Ritonavir | Cτ,ss of Darunavir | 1170 ng/mL | Geometric Coefficient of Variation 90.3 |
Comparison: relative bioavailability comparison (Faldaprevir+DRV/r : DRV/r) of Darunavir90% CI: [68.609, 112.63]ANOVA
Secondary
Tmax,ss of Darunavir
time from last dosing to maximum concentration of the analyte in plasma at steady state
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)
Population: PK set
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Darunavir+Ritonavir | Tmax,ss of Darunavir | 1.50 h | Full Range 33.9 |
| Faldaprevir+Darunavir+Ritonavir | Tmax,ss of Darunavir | 2.01 h | Full Range 37.3 |