Hepatitis C, Chronic
Conditions
Brief summary
The objective of this trial is to investigate tolerability, safety, pharmacokinetics and antiviral activity of BI 207127 NA in combination with BI 201335 NA and ribavirin for 8 weeks in Japanese treatment-naive patients with chronic GT-1 HCV infection.
Interventions
DRUGBI 207127 NA
one fix dose
DRUGpeginterferon
per package insert
DRUGRibavirin
per weight BID
DRUGBI 201335 NA
high dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C, diagnosed by positive anti-hepatitis C virus(HCV) antibodies and detected HCV ribonucleic acid(RNA) at screening in addition to: 1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or, 2. liver biopsy consistent with chronic HCV infection. * HCV infection of genotype 1 confirmed by genotypic testing at screening * Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection. * Plasma HCV RNA = 100,000 IU/mL at screening
Exclusion criteria
* Hepatitis C infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening * Human immunodeficiency virus (HIV) co-infection * Decompensated liver disease, or history of decompensated liver disease * Body weight \< 40 or \> 125 kg at screening * Hemoglobin \<12.0g/dL for women and \<13.0g/dL for men at screening * White blood cell count \<3000 cells/mm3 at screening * Absolute neutrophil count \< 1,500 cells/mm3 at screening * Platelet count \< 90,000 /mm3 at screening * Serum creatinine \> 1.5xUpper Limit of Normal range(ULN) or creatinine clearance =50 mL/min at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Drug-related Adverse Events | From first dose of study medication until 30 days after last dose of study medication, up to 199 days | Number of patients with investigator defined drug-related Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Virological Response at Week 8 | 8 weeks | Percentage of participants with plasma HCV RNA (hepatitis C virus ribonucleic acid ) level \<25 IU/mL (undetected or detected) at week 8. |
| Maximum Measured Concentration (Cmax) of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Maximum measured concentration of BI 207127 (Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). |
| Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Time from last dosing to the maximum concentration of Deleobuvir (BI 207127) in plasma after the morning dose of Nth day (Tmax,N). |
| Area Under the Curve (AUC) of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. |
| Maximum Measured Concentration (Cmax) of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Maximum measured concentration of Faldaprevir (BI 201335 ZW) in plasma following the morning dose of Nth day (Cmax,N). |
| Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Time from last dosing to the maximum concentration of Faldaprevir (BI 201335 ZW) in plasma after the morning dose of Nth day (Tmax,N). |
| Area Under the Curve (AUC) of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. |
| Maximum Measured Concentration (Cmax) of BI 208333 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Maximum measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). |
| Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Time from last dosing to the maximum concentration of BI 208333 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). |
| Area Under the Curve (AUC) of BI 208333 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. |
| Maximum Measured Concentration (Cmax) of CD 6168 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57 | Maximum measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). |
| Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Time from last dosing to the maximum concentration of CD 6168 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). |
| Area Under the Curve (AUC) of CD 6168 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. |
| Maximum Measured Concentration (Cmax) of CD 6168-AG | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57 | Maximum measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). AG=acylglucuronide. |
| Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Time from last dosing to the maximum concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). AG=acylglucuronide. |
| Area Under the Curve (AUC) of CD 6168-AG | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. AG=acylglucuronide. |
| Maximum Measured Concentration (Cmax) of RBV | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57 | Maximum measured concentration of ribavirin (RBV) in plasma following the morning dose of Nth day (Cmax,N). |
| Time From Last Dosing to the Maximum Concentration (Tmax) of RBV | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57 | Time from last dosing to the maximum concentration of ribavirin (RBV) in plasma after the morning dose of Nth day (Tmax,N). |
| Area Under the Curve (AUC) of RBV | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57 | Area under the concentration time curve (AUC) of ribavirin (RBV) in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. |
| Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of Deleobuvir versus itself (RA,Cmax,Met,ss). |
| AUC Accumulation Ratio of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of Deleobuvir versus itself (RA,AUC,Met,ss). |
| Mean Residence Time (MRTpo,ss) of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57 | Mean residence time of BI 207127 (Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). |
| Apparent Clearance (CL/F,ss) of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57 | Apparent clearance of BI 207127 (Deleobuvir) in plasma following extravascular administration on the 57th day (CL/F,ss). |
| Predose Measured Concentration of Deleobuvir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57 | Predose measured concentration of BI 207127 (Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). |
| Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N). |
| AUC Accumulation Ratio of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N). |
| Mean Residence Time (MRTpo,ss) of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57 | Mean residence time of Faldaprevir (BI 201335 ZW) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups. |
| Apparent Clearance (CL/F,ss) of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57 | Apparent clearance of Faldaprevir (BI 201335 ZW) in plasma following extravascular administration on the 57th day (CL/F,ss). |
| Predose Measured Concentration of Faldaprevir | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57 | Predose measured concentration of Faldaprevir (BI 201335 ZW) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). |
| Cmax Accumulation Ratio of BI 208333 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of BI 208333 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). |
| AUC Accumulation Ratio of BI 208333 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of BI 208333 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). |
| Mean Residence Time (MRTpo,ss) of BI 208333 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57 | Mean residence time of BI 208333 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups. |
| Predose Measured Concentration of BI 208333 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57 | Predose measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). |
| Cmax Accumulation Ratio of CD 6168 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). |
| AUC Accumulation Ratio of CD 6168 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). |
| Mean Residence Time (MRTpo,ss) of CD 6168 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57 | Mean residence time of CD 6168 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups. |
| Predose Measured Concentration of CD 6168 | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57 | Predose measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). |
| Cmax Accumulation Ratio of CD 6168-AG | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168-AG versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). AG=acylglucuronide. |
| AUC Accumulation Ratio of CD 6168-AG | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57 | Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168-AG versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). AG=acylglucuronide. |
| Mean Residence Time (MRTpo,ss) of CD 6168-AG | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57 | Mean residence time of CD 6168-AG (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). AG=acylglucuronide. This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups. |
| Percentage of Participants With Virological Response at Week 4 | 4 weeks | Percentage of participants with plasma HCV RNA (hepatitis C virus (HCV) ribonucleic acid (RNA)) level \<25 IU/mL (undetected or detected) at week 4. |
| AUC Accumulation Ratio of RBV | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57 | Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the 57th day and after the first dose (RA,AUC,57). |
| Cmax Accumulation Ratio (RA,Cmax,57) of RBV | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57 | Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the 57th day and after the first dose (RA,Cmax,57). |
| Mean Residence Time (MRTpo,ss) of RBV | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on day 57 | Mean residence time of ribavirin (RBV) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups. |
| Predose Measured Concentration of RBV | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 11 and 57 | Predose measured concentration of ribavirin (RBV) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). |
| Predose Measured Concentration of CD 6168-AG | 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57 | Predose measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). AG=acylglucuronide. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV). | 12 |
| 600mg Deleobuvir and 120mg Faldaprevir Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV). | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1: Faldap/Del/RBV | Adverse Event | 1 | 1 |
| Treatment Period 2: Faldap/PegIFN/RBV | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | 600mg Deleobuvir and 80mg Faldaprevir | 600mg Deleobuvir and 120mg Faldaprevir | Total |
|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 7.38 | 55.5 years STANDARD_DEVIATION 8.42 | 56.5 years STANDARD_DEVIATION 7.85 |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 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 | 12 / 12 | 13 / 13 | 11 / 11 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 | 1 / 11 | 0 / 12 |
Outcome results
Primary
Number of Patients With Drug-related Adverse Events
Number of patients with investigator defined drug-related Adverse Events
Time frame: From first dose of study medication until 30 days after last dose of study medication, up to 199 days
Population: Treated Set which included all patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Number of Patients With Drug-related Adverse Events | 12 participants |
| 600mg Deleobuvir and 120mg Faldaprevir | Number of Patients With Drug-related Adverse Events | 13 participants |
Secondary
Apparent Clearance (CL/F,ss) of Deleobuvir
Apparent clearance of BI 207127 (Deleobuvir) in plasma following extravascular administration on the 57th day (CL/F,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Population: Pharmacokinetic (PK) analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data. Analysis includes patients with available data for this parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Apparent Clearance (CL/F,ss) of Deleobuvir | 8.25 Litres per hour | Geometric Coefficient of Variation 102 |
| 600mg Deleobuvir and 120mg Faldaprevir | Apparent Clearance (CL/F,ss) of Deleobuvir | 2.81 Litres per hour | Geometric Coefficient of Variation 64.8 |
Secondary
Apparent Clearance (CL/F,ss) of Faldaprevir
Apparent clearance of Faldaprevir (BI 201335 ZW) in plasma following extravascular administration on the 57th day (CL/F,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data. Analysis includes patients with available data for this parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Apparent Clearance (CL/F,ss) of Faldaprevir | 22.7 mL/min | Geometric Coefficient of Variation 114 |
| 600mg Deleobuvir and 120mg Faldaprevir | Apparent Clearance (CL/F,ss) of Faldaprevir | 6.87 mL/min | Geometric Coefficient of Variation 78.5 |
Secondary
Area Under the Curve (AUC) of BI 208333
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of BI 208333 | Day 1 (N=9, 12) | 19900 nmol*h/L | Geometric Coefficient of Variation 67.5 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of BI 208333 | Day 11 (N=11, 12) | 94200 nmol*h/L | Geometric Coefficient of Variation 137 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of BI 208333 | Day 57 (N=10, 13) | 38400 nmol*h/L | Geometric Coefficient of Variation 109 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of BI 208333 | Day 1 (N=9, 12) | 26000 nmol*h/L | Geometric Coefficient of Variation 69.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of BI 208333 | Day 11 (N=11, 12) | 210000 nmol*h/L | Geometric Coefficient of Variation 82.9 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of BI 208333 | Day 57 (N=10, 13) | 141000 nmol*h/L | Geometric Coefficient of Variation 112 |
Secondary
Area Under the Curve (AUC) of CD 6168
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of CD 6168 | Day 1 (N=8, 10) | 11200 nmol*h/L | Geometric Coefficient of Variation 82.7 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of CD 6168 | Day 11 (N=11, 12) | 111000 nmol*h/L | Geometric Coefficient of Variation 177 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of CD 6168 | Day 57 (N=10, 12) | 61400 nmol*h/L | Geometric Coefficient of Variation 157 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of CD 6168 | Day 1 (N=8, 10) | 13200 nmol*h/L | Geometric Coefficient of Variation 75.1 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of CD 6168 | Day 11 (N=11, 12) | 234000 nmol*h/L | Geometric Coefficient of Variation 47.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of CD 6168 | Day 57 (N=10, 12) | 191000 nmol*h/L | Geometric Coefficient of Variation 73.3 |
Secondary
Area Under the Curve (AUC) of CD 6168-AG
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. AG=acylglucuronide.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of CD 6168-AG | Day 1 | NA nmol*h/L | — |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of CD 6168-AG | Day 11 (N=11, 12) | 6460 nmol*h/L | Geometric Coefficient of Variation 152 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of CD 6168-AG | Day 57 (N=10, 12) | 4110 nmol*h/L | Geometric Coefficient of Variation 122 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of CD 6168-AG | Day 1 | NA nmol*h/L | — |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of CD 6168-AG | Day 11 (N=11, 12) | 20700 nmol*h/L | Geometric Coefficient of Variation 76.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of CD 6168-AG | Day 57 (N=10, 12) | 17700 nmol*h/L | Geometric Coefficient of Variation 87.2 |
Secondary
Area Under the Curve (AUC) of Deleobuvir
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of Deleobuvir | Day 1 (N=9, 12) | 77500 nmol*h/L | Geometric Coefficient of Variation 57 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of Deleobuvir | Day 11 (N=11, 12) | 216000 nmol*h/L | Geometric Coefficient of Variation 104 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of Deleobuvir | Day 57 (N=10, 13) | 111000 nmol*h/L | Geometric Coefficient of Variation 102 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of Deleobuvir | Day 1 (N=9, 12) | 118000 nmol*h/L | Geometric Coefficient of Variation 59.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of Deleobuvir | Day 11 (N=11, 12) | 404000 nmol*h/L | Geometric Coefficient of Variation 52.3 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of Deleobuvir | Day 57 (N=10, 13) | 326000 nmol*h/L | Geometric Coefficient of Variation 64.8 |
Secondary
Area Under the Curve (AUC) of Faldaprevir
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of Faldaprevir | Day 1 (N=9, 9) | 42900 ng*h/mL | Geometric Coefficient of Variation 53 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of Faldaprevir | Day 11 (N=11, 10) | 119000 ng*h/mL | Geometric Coefficient of Variation 113 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of Faldaprevir | Day 57 (N=10, 11) | 58700 ng*h/mL | Geometric Coefficient of Variation 115 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of Faldaprevir | Day 1 (N=9, 9) | 107000 ng*h/mL | Geometric Coefficient of Variation 36.4 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of Faldaprevir | Day 11 (N=11, 10) | 360000 ng*h/mL | Geometric Coefficient of Variation 50.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of Faldaprevir | Day 57 (N=10, 11) | 291000 ng*h/mL | Geometric Coefficient of Variation 78.5 |
Secondary
Area Under the Curve (AUC) of RBV
Area under the concentration time curve (AUC) of ribavirin (RBV) in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of RBV | Day 1 (N=9, 13) | 3410 ng*h/mL | Geometric Coefficient of Variation 19 |
| 600mg Deleobuvir and 80mg Faldaprevir | Area Under the Curve (AUC) of RBV | Day 57 (N=8, 10) | 25700 ng*h/mL | Geometric Coefficient of Variation 22.7 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of RBV | Day 1 (N=9, 13) | 3730 ng*h/mL | Geometric Coefficient of Variation 57.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | Area Under the Curve (AUC) of RBV | Day 57 (N=8, 10) | 27600 ng*h/mL | Geometric Coefficient of Variation 39.1 |
Secondary
AUC Accumulation Ratio of BI 208333
Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of BI 208333 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of BI 208333 | RA,AUC,11 (N=11, 12) | 4.16 Ratio | Geometric Coefficient of Variation 106 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of BI 208333 | RA,AUC,57 (N=110 13) | 1.48 Ratio | Geometric Coefficient of Variation 137 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of BI 208333 | RA,AUC,tau,Met,ss (N=10, 13) | 0.345 Ratio | Geometric Coefficient of Variation 24.1 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of BI 208333 | RA,AUC,11 (N=11, 12) | 8.10 Ratio | Geometric Coefficient of Variation 39.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of BI 208333 | RA,AUC,57 (N=110 13) | 4.92 Ratio | Geometric Coefficient of Variation 60.9 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of BI 208333 | RA,AUC,tau,Met,ss (N=10, 13) | 0.431 Ratio | Geometric Coefficient of Variation 57.9 |
Secondary
AUC Accumulation Ratio of CD 6168
Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of CD 6168 | RA,AUC,11 (N=10, 10) | 9.57 Ratio | Geometric Coefficient of Variation 74.9 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of CD 6168 | RA,AUC,57 (N=9, 11) | 5.14 Ratio | Geometric Coefficient of Variation 106 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of CD 6168 | RA,AUC,tau,Met,ss (N=10, 12) | 0.552 Ratio | Geometric Coefficient of Variation 48 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of CD 6168 | RA,AUC,11 (N=10, 10) | 17.0 Ratio | Geometric Coefficient of Variation 75.4 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of CD 6168 | RA,AUC,57 (N=9, 11) | 14.2 Ratio | Geometric Coefficient of Variation 92.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of CD 6168 | RA,AUC,tau,Met,ss (N=10, 12) | 0.600 Ratio | Geometric Coefficient of Variation 24.6 |
Secondary
AUC Accumulation Ratio of CD 6168-AG
Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168-AG versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). AG=acylglucuronide.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of CD 6168-AG | RA,AUC,11 (N=11, 8) | 16.7 Ratio | Geometric Coefficient of Variation 122 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of CD 6168-AG | RA,AUC,57 (N=9, 8) | 8.06 Ratio | Geometric Coefficient of Variation 163 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of CD 6168-AG | RA,AUC,tau,Met,ss (N=10, 12) | 0.0369 Ratio | Geometric Coefficient of Variation 36.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of CD 6168-AG | RA,AUC,11 (N=11, 8) | NA Ratio | — |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of CD 6168-AG | RA,AUC,57 (N=9, 8) | NA Ratio | — |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of CD 6168-AG | RA,AUC,tau,Met,ss (N=10, 12) | 0.0557 Ratio | Geometric Coefficient of Variation 46.2 |
Secondary
AUC Accumulation Ratio of Deleobuvir
Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of Deleobuvir versus itself (RA,AUC,Met,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: Pharmacokinetic (PK) analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of Deleobuvir | RA,AUC,11 (N=11, 12) | 2.60 Ratio | Geometric Coefficient of Variation 62.5 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of Deleobuvir | RA,AUC,57 (N=10, 13) | 1.21 Ratio | Geometric Coefficient of Variation 71.3 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of Deleobuvir | RA,AUC,tau,Met,ss (N=10, 13) | 1.00 Ratio | Geometric Coefficient of Variation 0 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of Deleobuvir | RA,AUC,11 (N=11, 12) | 3.43 Ratio | Geometric Coefficient of Variation 43.3 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of Deleobuvir | RA,AUC,57 (N=10, 13) | 2.74 Ratio | Geometric Coefficient of Variation 58.9 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of Deleobuvir | RA,AUC,tau,Met,ss (N=10, 13) | 1.00 Ratio | Geometric Coefficient of Variation 0 |
Secondary
AUC Accumulation Ratio of Faldaprevir
Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of Faldaprevir | RA, AUC,11 (N=11, 9) | 2.88 Ratio | Geometric Coefficient of Variation 73 |
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of Faldaprevir | RA,AUC,57 (N=10, 9) | 1.28 Ratio | Geometric Coefficient of Variation 96.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of Faldaprevir | RA, AUC,11 (N=11, 9) | 3.31 Ratio | Geometric Coefficient of Variation 43.3 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of Faldaprevir | RA,AUC,57 (N=10, 9) | 2.26 Ratio | Geometric Coefficient of Variation 57.6 |
Secondary
AUC Accumulation Ratio of RBV
Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the 57th day and after the first dose (RA,AUC,57).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data. Analysis includes patients with available data for this parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | AUC Accumulation Ratio of RBV | 8.03 Ratio | Geometric Coefficient of Variation 17.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | AUC Accumulation Ratio of RBV | 6.89 Ratio | Geometric Coefficient of Variation 60.8 |
Secondary
Cmax Accumulation Ratio of BI 208333
Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of BI 208333 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of BI 208333 | RA,Cmax,11 (N=11, 12) | 3.82 Ratio | Geometric Coefficient of Variation 81.2 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of BI 208333 | RA,Cmax,57 (N=11, 13) | 1.60 Ratio | Geometric Coefficient of Variation 85.2 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of BI 208333 | RA,Cmax,Met,ss (N=11, 13) | 0.345 Ratio | Geometric Coefficient of Variation 24.1 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of BI 208333 | RA,Cmax,11 (N=11, 12) | 5.73 Ratio | Geometric Coefficient of Variation 36.2 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of BI 208333 | RA,Cmax,57 (N=11, 13) | 3.99 Ratio | Geometric Coefficient of Variation 61.2 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of BI 208333 | RA,Cmax,Met,ss (N=11, 13) | 0.349 Ratio | Geometric Coefficient of Variation 64 |
Secondary
Cmax Accumulation Ratio of CD 6168
Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of CD 6168 | RA,Cmax,11 (N=10, 12) | 8.34 Ratio | Geometric Coefficient of Variation 78.5 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of CD 6168 | RA,Cmax,57 (N=11, 13) | 4.90 Ratio | Geometric Coefficient of Variation 75.4 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of CD 6168 | RA,Cmax,Met,ss (N=11, 13) | 0.380 Ratio | Geometric Coefficient of Variation 47.7 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of CD 6168 | RA,Cmax,11 (N=10, 12) | 12.2 Ratio | Geometric Coefficient of Variation 71.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of CD 6168 | RA,Cmax,57 (N=11, 13) | 10.9 Ratio | Geometric Coefficient of Variation 82.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of CD 6168 | RA,Cmax,Met,ss (N=11, 13) | 0.500 Ratio | Geometric Coefficient of Variation 34.6 |
Secondary
Cmax Accumulation Ratio of CD 6168-AG
Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168-AG versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). AG=acylglucuronide.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of CD 6168-AG | RA,Cmax,11 (N=11, 8) | 10.8 Ratio | Geometric Coefficient of Variation 105 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of CD 6168-AG | RA,Cmax,57 (N=11, 13) | 7.11 Ratio | Geometric Coefficient of Variation 109 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio of CD 6168-AG | RA,Cmax,Met,ss (N=11, 13) | 0.0242 Ratio | Geometric Coefficient of Variation 45.4 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of CD 6168-AG | RA,Cmax,11 (N=11, 8) | NA Ratio | — |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of CD 6168-AG | RA,Cmax,57 (N=11, 13) | 17.2 Ratio | Geometric Coefficient of Variation 89.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio of CD 6168-AG | RA,Cmax,Met,ss (N=11, 13) | 0.0424 Ratio | Geometric Coefficient of Variation 53.9 |
Secondary
Cmax Accumulation Ratio (RA,Cmax,57) of RBV
Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the 57th day and after the first dose (RA,Cmax,57).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data. Analysis includes patients with available data for this parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,57) of RBV | 5.05 Ratio | Geometric Coefficient of Variation 22.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,57) of RBV | 4.89 Ratio | Geometric Coefficient of Variation 67.6 |
Secondary
Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir
Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of Deleobuvir versus itself (RA,Cmax,Met,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: Pharmacokinetic (PK) analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir | RA,Cmax,11 (N=11, 12) | 2.33 Ratio | Geometric Coefficient of Variation 50.9 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir | RA,Cmax,57 (N=11, 13) | 1.46 Ratio | Geometric Coefficient of Variation 53.2 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir | RA,Cmax,Met,ss (N=11, 13) | 1.00 Ratio | Geometric Coefficient of Variation 0 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir | RA,Cmax,11 (N=11, 12) | 2.68 Ratio | Geometric Coefficient of Variation 47.3 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir | RA,Cmax,57 (N=11, 13) | 2.20 Ratio | Geometric Coefficient of Variation 53.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir | RA,Cmax,Met,ss (N=11, 13) | 1.00 Ratio | Geometric Coefficient of Variation 0 |
Secondary
Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir
Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir | RA,Cmax,11 (N=11, 12) | 2.72 Ratio | Geometric Coefficient of Variation 56.1 |
| 600mg Deleobuvir and 80mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir | RA,Cmax,57 (N=11, 13) | 1.51 Ratio | Geometric Coefficient of Variation 68 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir | RA,Cmax,11 (N=11, 12) | 3.17 Ratio | Geometric Coefficient of Variation 55.4 |
| 600mg Deleobuvir and 120mg Faldaprevir | Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir | RA,Cmax,57 (N=11, 13) | 3.00 Ratio | Geometric Coefficient of Variation 81.7 |
Secondary
Maximum Measured Concentration (Cmax) of BI 208333
Maximum measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of BI 208333 | Day 1 (N=9, 12) | 2600 nmol/L | Geometric Coefficient of Variation 64.2 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of BI 208333 | Day 11 (N=11, 12) | 11100 nmol/L | Geometric Coefficient of Variation 92.5 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of BI 208333 | Day 57 (N=11, 13) | 4630 nmol/L | Geometric Coefficient of Variation 74 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of BI 208333 | Day 1 (N=9, 12) | 3630 nmol/L | Geometric Coefficient of Variation 76.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of BI 208333 | Day 11 (N=11, 12) | 20800 nmol/L | Geometric Coefficient of Variation 80.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of BI 208333 | Day 57 (N=11, 13) | 14600 nmol/L | Geometric Coefficient of Variation 92.7 |
Secondary
Maximum Measured Concentration (Cmax) of CD 6168
Maximum measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168 | Day 1 (N=9, 12) | 1640 nmol/L | Geometric Coefficient of Variation 73.7 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168 | Day 11 (N=11, 12) | 12200 nmol/L | Geometric Coefficient of Variation 144 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168 | Day 57 (N=11, 13) | 7150 nmol/L | Geometric Coefficient of Variation 109 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168 | Day 1 (N=9, 12) | 1920 nmol/L | Geometric Coefficient of Variation 75.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168 | Day 11 (N=11, 12) | 23400 nmol/L | Geometric Coefficient of Variation 40.4 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168 | Day 57 (N=11, 13) | 21000 nmol/L | Geometric Coefficient of Variation 62.3 |
Secondary
Maximum Measured Concentration (Cmax) of CD 6168-AG
Maximum measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). AG=acylglucuronide.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168-AG | Day 1 (N=9, 12) | 73.7 nmol/L | Geometric Coefficient of Variation 81.3 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168-AG | Day 11 (N=11, 12) | 691 nmol/L | Geometric Coefficient of Variation 132 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168-AG | Day 57 (N=11, 13) | 455 nmol/L | Geometric Coefficient of Variation 97.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168-AG | Day 1 (N=9, 12) | 106 nmol/L | Geometric Coefficient of Variation 85.2 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168-AG | Day 11 (N=11, 12) | 2020 nmol/L | Geometric Coefficient of Variation 71.7 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of CD 6168-AG | Day 57 (N=11, 13) | 1780 nmol/L | Geometric Coefficient of Variation 75.3 |
Secondary
Maximum Measured Concentration (Cmax) of Deleobuvir
Maximum measured concentration of BI 207127 (Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: Pharmacokinetic (PK) analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of Deleobuvir | Day 1 (N=9, 12) | 12800 nmol/L | Geometric Coefficient of Variation 57.3 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of Deleobuvir | Day 11 (N=11, 12) | 30100 nmol/L | Geometric Coefficient of Variation 71.6 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of Deleobuvir | Day 57 (N=11, 13) | 18800 nmol/L | Geometric Coefficient of Variation 61 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of Deleobuvir | Day 1 (N=9, 12) | 18800 nmol/L | Geometric Coefficient of Variation 55.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of Deleobuvir | Day 11 (N=11, 12) | 50300 nmol/L | Geometric Coefficient of Variation 35.4 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of Deleobuvir | Day 57 (N=11, 13) | 41900 nmol/L | Geometric Coefficient of Variation 51.6 |
Secondary
Maximum Measured Concentration (Cmax) of Faldaprevir
Maximum measured concentration of Faldaprevir (BI 201335 ZW) in plasma following the morning dose of Nth day (Cmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of Faldaprevir | Day 1 (N=9, 12) | 3380 ng/mL | Geometric Coefficient of Variation 43.9 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of Faldaprevir | Day 11 (N=11, 12) | 8530 ng/mL | Geometric Coefficient of Variation 76 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of Faldaprevir | Day 57 (N=11, 13) | 4750 ng/mL | Geometric Coefficient of Variation 65.1 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of Faldaprevir | Day 1 (N=9, 12) | 6440 ng/mL | Geometric Coefficient of Variation 46.9 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of Faldaprevir | Day 11 (N=11, 12) | 20400 ng/mL | Geometric Coefficient of Variation 39.7 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of Faldaprevir | Day 57 (N=11, 13) | 18700 ng/mL | Geometric Coefficient of Variation 59 |
Secondary
Maximum Measured Concentration (Cmax) of RBV
Maximum measured concentration of ribavirin (RBV) in plasma following the morning dose of Nth day (Cmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of RBV | Day 1 (N=9, 13) | 537 ng/mL | Geometric Coefficient of Variation 27.1 |
| 600mg Deleobuvir and 80mg Faldaprevir | Maximum Measured Concentration (Cmax) of RBV | Day 57 (N=9, 11) | 2560 ng/mL | Geometric Coefficient of Variation 21.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of RBV | Day 1 (N=9, 13) | 601 ng/mL | Geometric Coefficient of Variation 58.1 |
| 600mg Deleobuvir and 120mg Faldaprevir | Maximum Measured Concentration (Cmax) of RBV | Day 57 (N=9, 11) | 2740 ng/mL | Geometric Coefficient of Variation 31.8 |
Secondary
Mean Residence Time (MRTpo,ss) of BI 208333
Mean residence time of BI 208333 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
Secondary
Mean Residence Time (MRTpo,ss) of CD 6168
Mean residence time of CD 6168 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
Secondary
Mean Residence Time (MRTpo,ss) of CD 6168-AG
Mean residence time of CD 6168-AG (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). AG=acylglucuronide. This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
Secondary
Mean Residence Time (MRTpo,ss) of Deleobuvir
Mean residence time of BI 207127 (Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Population: Pharmacokinetic (PK) analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data. Analysis includes patients with available data for this parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Mean Residence Time (MRTpo,ss) of Deleobuvir | 6.65 hours | Geometric Coefficient of Variation 39 |
| 600mg Deleobuvir and 120mg Faldaprevir | Mean Residence Time (MRTpo,ss) of Deleobuvir | 12.6 hours | Geometric Coefficient of Variation 52.2 |
Secondary
Mean Residence Time (MRTpo,ss) of Faldaprevir
Mean residence time of Faldaprevir (BI 201335 ZW) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
Secondary
Mean Residence Time (MRTpo,ss) of RBV
Mean residence time of ribavirin (RBV) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on day 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
Secondary
Percentage of Participants With Virological Response at Week 4
Percentage of participants with plasma HCV RNA (hepatitis C virus (HCV) ribonucleic acid (RNA)) level \<25 IU/mL (undetected or detected) at week 4.
Time frame: 4 weeks
Population: Full analysis set which included all patients with at least 1 on-treatment value of HCV RNA viral load
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Percentage of Participants With Virological Response at Week 4 | 91.7 percentage of participants |
| 600mg Deleobuvir and 120mg Faldaprevir | Percentage of Participants With Virological Response at Week 4 | 92.3 percentage of participants |
Secondary
Percentage of Participants With Virological Response at Week 8
Percentage of participants with plasma HCV RNA (hepatitis C virus ribonucleic acid ) level \<25 IU/mL (undetected or detected) at week 8.
Time frame: 8 weeks
Population: Full analysis set which included all patients with at least 1 on-treatment value of HCV RNA viral load
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Percentage of Participants With Virological Response at Week 8 | 91.7 percentage of participants |
| 600mg Deleobuvir and 120mg Faldaprevir | Percentage of Participants With Virological Response at Week 8 | 100.0 percentage of participants |
Secondary
Predose Measured Concentration of BI 208333
Predose measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of BI 208333 | Cpre,11 (N=9, 13) | 7450 nmol/L | Geometric Coefficient of Variation 186 |
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of BI 208333 | Cpre,ss (N=11, 13) | 1630 nmol/L | Geometric Coefficient of Variation 241 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of BI 208333 | Cpre,11 (N=9, 13) | 16800 nmol/L | Geometric Coefficient of Variation 87.1 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of BI 208333 | Cpre,ss (N=11, 13) | 10700 nmol/L | Geometric Coefficient of Variation 125 |
Secondary
Predose Measured Concentration of CD 6168
Predose measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of CD 6168 | Cpre,11 (N=9, 13) | 9610 nmol/L | Geometric Coefficient of Variation 246 |
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of CD 6168 | Cpre,ss (N=11, 13) | 3190 nmol/L | Geometric Coefficient of Variation 279 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of CD 6168 | Cpre,11 (N=9, 13) | 17600 nmol/L | Geometric Coefficient of Variation 76.7 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of CD 6168 | Cpre,ss (N=11, 13) | 13100 nmol/L | Geometric Coefficient of Variation 82.6 |
Secondary
Predose Measured Concentration of CD 6168-AG
Predose measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). AG=acylglucuronide.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of CD 6168-AG | Cpre,11 (N=9, 13) | 566 nmol/L | Geometric Coefficient of Variation 154 |
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of CD 6168-AG | Cpre,ss (N=11, 13) | 211 nmol/L | Geometric Coefficient of Variation 197 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of CD 6168-AG | Cpre,11 (N=9, 13) | 1630 nmol/L | Geometric Coefficient of Variation 73.9 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of CD 6168-AG | Cpre,ss (N=11, 13) | 1350 nmol/L | Geometric Coefficient of Variation 82.8 |
Secondary
Predose Measured Concentration of Deleobuvir
Predose measured concentration of BI 207127 (Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57
Population: Pharmacokinetic (PK) analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of Deleobuvir | Cpre,11 (N=9, 12) | 10700 nmol/L | Geometric Coefficient of Variation 217 |
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of Deleobuvir | Cpre,ss (N=11, 13) | 3280 nmol/L | Geometric Coefficient of Variation 234 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of Deleobuvir | Cpre,ss (N=11, 13) | 16599 nmol/L | Geometric Coefficient of Variation 109 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of Deleobuvir | Cpre,11 (N=9, 12) | 23500 nmol/L | Geometric Coefficient of Variation 61.1 |
Secondary
Predose Measured Concentration of Faldaprevir
Predose measured concentration of Faldaprevir (BI 201335 ZW) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of Faldaprevir | Cpre,11 (N=9, 12) | 4250 ng/mL | Geometric Coefficient of Variation 143 |
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of Faldaprevir | Cpre,ss (N=11, 12) | 1540 ng/mL | Geometric Coefficient of Variation 176 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of Faldaprevir | Cpre,11 (N=9, 12) | 13800 ng/mL | Geometric Coefficient of Variation 47.5 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of Faldaprevir | Cpre,ss (N=11, 12) | 9980 ng/mL | Geometric Coefficient of Variation 92.6 |
Secondary
Predose Measured Concentration of RBV
Predose measured concentration of ribavirin (RBV) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of RBV | Cpre,11 (N=9, 13) | 1400 ng/mL | Geometric Coefficient of Variation 26.8 |
| 600mg Deleobuvir and 80mg Faldaprevir | Predose Measured Concentration of RBV | Cpre,ss (N=10, 12) | 2080 ng/mL | Geometric Coefficient of Variation 25.6 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of RBV | Cpre,11 (N=9, 13) | 1290 ng/mL | Geometric Coefficient of Variation 31.8 |
| 600mg Deleobuvir and 120mg Faldaprevir | Predose Measured Concentration of RBV | Cpre,ss (N=10, 12) | 2110 ng/mL | Geometric Coefficient of Variation 38.6 |
Secondary
Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333
Time from last dosing to the maximum concentration of BI 208333 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 | Day 1 (N=9, 12) | 6.00 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 | Day 11 (N=11, 12) | 5.90 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 | Day 57 (N=11, 13) | 5.97 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 | Day 1 (N=9, 12) | 7.80 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 | Day 11 (N=11, 12) | 3.99 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 | Day 57 (N=11, 13) | 5.98 hours |
Secondary
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168
Time from last dosing to the maximum concentration of CD 6168 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 | Day 1 (N=9, 12) | 8.00 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 | Day 11 (N=11, 12) | 3.95 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 | Day 57 (N=11, 13) | 5.83 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 | Day 1 (N=9, 12) | 9.81 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 | Day 11 (N=11, 12) | 3.94 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 | Day 57 (N=11, 13) | 4.10 hours |
Secondary
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG
Time from last dosing to the maximum concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). AG=acylglucuronide.
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG | Day 1 (N=9, 12) | 8.00 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG | Day 11 (N=11, 12) | 5.90 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG | Day 57 (N=11, 13) | 5.85 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG | Day 1 (N=9, 12) | 9.93 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG | Day 11 (N=11, 12) | 4.96 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG | Day 57 (N=11, 13) | 6.08 hours |
Secondary
Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir
Time from last dosing to the maximum concentration of Deleobuvir (BI 207127) in plasma after the morning dose of Nth day (Tmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir | Day 1 (N=9, 12) | 3.97 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir | Day 11 (N=11, 12) | 3.92 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir | Day 57 (N=11, 13) | 4.00 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir | Day 1 (N=9, 12) | 5.03 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir | Day 11 (N=11, 12) | 3.94 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir | Day 57 (N=11, 13) | 3.98 hours |
Secondary
Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir
Time from last dosing to the maximum concentration of Faldaprevir (BI 201335 ZW) in plasma after the morning dose of Nth day (Tmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir | Day 1 (N=9, 12) | 3.97 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir | Day 11 (N=11, 12) | 3.92 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir | Day 57 (N=11, 13) | 3.92 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir | Day 1 (N=9, 12) | 5.98 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir | Day 11 (N=11, 12) | 4.00 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir | Day 57 (N=11, 13) | 3.97 hours |
Secondary
Time From Last Dosing to the Maximum Concentration (Tmax) of RBV
Time from last dosing to the maximum concentration of ribavirin (RBV) in plasma after the morning dose of Nth day (Tmax,N).
Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of RBV | Day 1 (N=9, 13) | 2.00 hours |
| 600mg Deleobuvir and 80mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of RBV | Day 57 (N=9, 11) | 2.08 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of RBV | Day 1 (N=9, 13) | 3.95 hours |
| 600mg Deleobuvir and 120mg Faldaprevir | Time From Last Dosing to the Maximum Concentration (Tmax) of RBV | Day 57 (N=9, 11) | 2.03 hours |