Hepatitis C
Conditions
Brief summary
The main objective of this study is to investigate the influence of mild, moderate and severe renal impairment on the pharmacokinetics and safety of BI 201335 in comparison to a control group with normal renal function after single dose of BI 201335.
Interventions
DRUGBI 201335
Relevant treatment dose capsule (A) for oral administration
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Male and female healthy subjects with normal renal function and subjects with impaired renal function in relatively good health
Exclusion criteria
Any relevant deviation from healthy conditions for healthy volunteers or significant diseases other than renal impairment for the renal impaired subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-∞ | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00,16:00, 24:00, 36:00, 48:00, 72:00, 96:00, 120:00, 144:00 hours (h) after administration | area under the concentration time curve of Faldaprevir in plasma over the time interval from 0 to infinity. In this endpoint, the data of AUC0-∞ show inter-individual variabilities. |
| Cmax | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00,16:00, 24:00, 36:00, 48:00, 72:00, 96:00, 120:00, 144:00h after administration | maximum concentration of Faldaprevir in plasma. In this endpoint, the data of Cmax show inter-individual variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | from drug administration up to 2 weeks | Clinical relevant abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. |
| Number of Participants With Drug Related Adverse Events | drug administration until end-of-study examination (7 to 14 days after drug administration) | number of participants with investigator-defined drug related adverse events. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Renal Function Capsule for oral administration (120 mg Faldaprevir)
subjects with estimated glomerular filtration rate \>= 90 mL/min/1.73m2 | 8 |
| Mild Renal Impairment Capsule for oral administration (120 mg Faldaprevir)
subjects with estimated glomerular filtration rate 60-89 mL/min/1.73m2 | 8 |
| Moderate Renal Impairment Capsule for oral administration (120 mg Faldaprevir)
subjects with estimated glomerular filtration rate 30-59 mL/min/1.73m2 | 8 |
| Severe Renal Impairment Capsule for oral administration (120 mg Faldaprevir)
subjects with estimated glomerular filtration rate 15-29 mL/min/1.73m2 | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Severe Renal Impairment | Total | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment |
|---|---|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 9.5 | 61.4 years STANDARD_DEVIATION 8.2 | 62.3 years STANDARD_DEVIATION 2.1 | 58.8 years STANDARD_DEVIATION 9.3 | 67.1 years STANDARD_DEVIATION 7.5 |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 2 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 21 Participants | 6 Participants | 5 Participants | 5 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 | 5 / 8 | 8 / 8 | 5 / 8 | 7 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
AUC0-∞
area under the concentration time curve of Faldaprevir in plasma over the time interval from 0 to infinity. In this endpoint, the data of AUC0-∞ show inter-individual variabilities.
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00,16:00, 24:00, 36:00, 48:00, 72:00, 96:00, 120:00, 144:00 hours (h) after administration
Population: Pharmacokinetic (PK) set: This subject set included all subjects in the treated set who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK, and who did not vomit at or before 2 times median tmax of unmetabolised faldaprevir.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | AUC0-∞ | 76500 ng*h/mL | Geometric Coefficient of Variation 95.7 |
| Mild Renal Impairment | AUC0-∞ | 86900 ng*h/mL | Geometric Coefficient of Variation 89.8 |
| Moderate Renal Impairment | AUC0-∞ | 136000 ng*h/mL | Geometric Coefficient of Variation 67.2 |
| Severe Renal Impairment | AUC0-∞ | 129000 ng*h/mL | Geometric Coefficient of Variation 98.8 |
Comparison: relative bioavailability comparison mild : normal90% CI: [41.58, 310.17]ANOVA
Comparison: relative bioavailability comparison moderate : normal90% CI: [85.23, 373.03]ANOVA
Comparison: relative bioavailability comparison severe : normal90% CI: [73.19, 391.17]ANOVA
Primary
Cmax
maximum concentration of Faldaprevir in plasma. In this endpoint, the data of Cmax show inter-individual variabilities.
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00,16:00, 24:00, 36:00, 48:00, 72:00, 96:00, 120:00, 144:00h after administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Cmax | 3810 ng/mL | Geometric Coefficient of Variation 80.7 |
| Mild Renal Impairment | Cmax | 4080 ng/mL | Geometric Coefficient of Variation 144 |
| Moderate Renal Impairment | Cmax | 6680 ng/mL | Geometric Coefficient of Variation 63.2 |
| Severe Renal Impairment | Cmax | 4600 ng/mL | Geometric Coefficient of Variation 135 |
Comparison: relative bioavailability comparison mild : normal90% CI: [35.16, 327.01]ANOVA
Comparison: relative bioavailability comparison moderate : normal90% CI: [89.55, 344.06]ANOVA
Comparison: relative bioavailability comparison severe : normal90% CI: [47.257, 309.736]ANOVA
Secondary
Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG
Clinical relevant abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Time frame: from drug administration up to 2 weeks
Population: treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Renal Function | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | Blood bilirubin increased | 0 participants |
| Normal Renal Function | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | blood pressure systolic increased | 0 participants |
| Mild Renal Impairment | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | Blood bilirubin increased | 0 participants |
| Mild Renal Impairment | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | blood pressure systolic increased | 0 participants |
| Moderate Renal Impairment | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | blood pressure systolic increased | 1 participants |
| Moderate Renal Impairment | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | Blood bilirubin increased | 0 participants |
| Severe Renal Impairment | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | blood pressure systolic increased | 0 participants |
| Severe Renal Impairment | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG | Blood bilirubin increased | 1 participants |
Secondary
Number of Participants With Drug Related Adverse Events
number of participants with investigator-defined drug related adverse events.
Time frame: drug administration until end-of-study examination (7 to 14 days after drug administration)
Population: treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Renal Function | Number of Participants With Drug Related Adverse Events | 5 participants |
| Mild Renal Impairment | Number of Participants With Drug Related Adverse Events | 8 participants |
| Moderate Renal Impairment | Number of Participants With Drug Related Adverse Events | 5 participants |
| Severe Renal Impairment | Number of Participants With Drug Related Adverse Events | 7 participants |