Hepatitis C, Pharmacokinetics
Conditions
Brief summary
The current Standard of Care (SOC) for chronic HCV infection, which is pegylated interferon-alfa as combination therapy with ribavirin for 24-48 weeks of treatment, is effective in only part of the patients and is often associated with severe adverse effects leading to discontinuation of treatment and dose modifications. A number of compounds with direct activity are currently under clinical development, incl. BI 201335. BI 201335 works by preventing the Hepatitis C virus from replicating by binding to the HCV protease (enzyme). The main purpose of this clinical trial with BI 201335 is to see how well BI 201335 works and how safe BI 201335 is to use daily in combination with PegIFN and RBV in HCV infected patients
Interventions
DRUGBI 201335 NA low placebo
Placebo
DRUGBI 201335 NA high
BI 201335 NA high
DRUGBI 201335 NA low
BI 201335 NA
DRUGBI 201335 NA high placebo
placebo
DRUGPlacebo
DRUGribavirin (RBV)
ribavirin (RBV)
DRUGpegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* chronic HCV genotype-1; * high viral load
Exclusion criteria
* Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening * Previous treatment with protease inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy | 4 weeks | Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator. |
| Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | 4 weeks | Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in triple combination therapy for treatment naive patients and treatment experienced patients. |
| Assessment of Tolerability in Triple Combination Therapy | 4 weeks | An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HCV Viral Load | baseline and week 4 | Change form baseline in HCV viral load (log10) after 4 weeks |
| Day 28 Virologic Response | 4 weeks | Number of patients with HCV viral load reduction \>= 2 log10 at Week 4 |
| Early Virological Response (EVR) | 12 Weeks | Number of patients with reduction \>= 2 log10 in plasma HCV RNA level at Week 12 |
| Complete Early Virological Response (cEVR) | 12 weeks | Number of patients with plasma HCV RNA level BLD at Week 12 |
| End of Treatment Response (ETR) | 48 weeks | Number of patients with plasma HCV RNA level BLD at week 48 |
| Sustained Virologic Response (SVR) | 72 weeks | Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion |
| Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV | 44 weeks | Drug-related AEs in SOC treatment period were defined as those whose causal relationship with any one of the investigational products was considered by the investigator. |
| Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | 44 weeks | Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in SOC period for treatment naive patients and treatment experienced patients. |
| Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | 44 weeks | An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV. |
| AUCτ,1 for BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose | Area under the curve (AUC) concentration after the first dose of BI 201335 ZW |
| Cmax of BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose | Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a |
| AUCτ,ss of BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | AUC at steady state after 4 weeks combination of the last dose |
| Cmax,ss of BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | Maximum concentration of BI 201335 ZW at steady state |
| Week 2 Virological Response (W2VR) | 2 weeks | Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ)) |
| Cmax of RBV | -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose | Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a |
| AUCτ,ss of RBV | -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose | Area under the plasma concentration curve of RBV after the multiple oral administration of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state |
| Cmax,ss of RBV | -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose | Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state |
| Tmax for BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose | Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a |
| Tmax for RBV | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose | Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a |
| Tmax, ss for BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | Time from last dosing to the maximum plasma concentration (tmax) of BI 201335 ZW after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state |
| Tmax, ss for RBV | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | Time to the maximum plasma concentration (tmax) of RBV after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state |
| t1/2,ss for BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | terminal half-life of the analyte in plasma at steady state (t1/2,ss) |
| Cmin,ss for BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state |
| Cmin,ss for RBV | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state |
| Cavg for BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | average plasma concentration (Cavg) of BI 201335 ZW |
| Cavg for RBV | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | average plasma concentration (Cavg) of RBV |
| CL/F,ss for BI 201335 ZW | 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose | apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration |
| AUCτ,1 for Ribavirin (RBV) | -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose | Area under the plasma concentration curve of RBV after the first dose of placebo or BI 201335 NA with with RBV and PegIFN alfa-2a |
| Week 4 Virological Response (W4VR) | 4 weeks | Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ)) |
| Rapid Virological Response (RVR) | 4 weeks | Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4) |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo in TN Patients Matching placebo to BI 201335 NA with PegIFN/RBV in TN patients | 4 |
| BI 201335 NA Low TN Patients receive a capsule containing low dose of BI 201335 NA (120 mg q.d.) with PegIFN/RBV in TN patients | 6 |
| BI 201335 NA High TN Patients receive a capsule containing high dose of BI 201335 NA (240 mg q.d.). with PegIFN/RBV in TN patients | 6 |
| BI 201335 NA High TE Patients receive a capsule containing high dose of BI 201335 NA (240 mg q.d.) with PegIFN/RBV in TE patients | 6 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study Standard of Care | Lack of Efficacy | 0 | 0 | 1 | 1 |
| Overall Study Standard of Care | Other | 0 | 0 | 0 | 1 |
| Overall Study Standard of Care | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Triple Treatment Combination Period | Adverse Event | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo in TN Patients | BI 201335 NA Low TN | BI 201335 NA High TN | BI 201335 NA High TE | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 6 | 48.0 years STANDARD_DEVIATION 13.5 | 56.0 years STANDARD_DEVIATION 9.2 | 58.0 years STANDARD_DEVIATION 8.3 | 53.9 years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 4 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 6 / 6 | 6 / 6 | 6 / 6 | 3 / 4 | 5 / 5 | 5 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 4 | 1 / 6 | 0 / 6 | 0 / 6 | 1 / 4 | 0 / 5 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Assessment of Tolerability in Triple Combination Therapy
An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV.
Time frame: 4 weeks
Population: The treated set (TS) consisted of all patients who were given study medication and were documented to have taken at least one dose of investigational products regardless of randomisation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Triple TN Placebo | Assessment of Tolerability in Triple Combination Therapy | Not Satisfactory | 1 participants |
| Triple TN Placebo | Assessment of Tolerability in Triple Combination Therapy | Satisfactory | 0 participants |
| Triple TN Placebo | Assessment of Tolerability in Triple Combination Therapy | Good | 3 participants |
| Triple TN Placebo | Assessment of Tolerability in Triple Combination Therapy | Bad | 0 participants |
| Triple TN 120 mg | Assessment of Tolerability in Triple Combination Therapy | Good | 5 participants |
| Triple TN 120 mg | Assessment of Tolerability in Triple Combination Therapy | Not Satisfactory | 0 participants |
| Triple TN 120 mg | Assessment of Tolerability in Triple Combination Therapy | Satisfactory | 1 participants |
| Triple TN 120 mg | Assessment of Tolerability in Triple Combination Therapy | Bad | 0 participants |
| Triple TN 240 mg | Assessment of Tolerability in Triple Combination Therapy | Good | 5 participants |
| Triple TN 240 mg | Assessment of Tolerability in Triple Combination Therapy | Satisfactory | 1 participants |
| Triple TN 240 mg | Assessment of Tolerability in Triple Combination Therapy | Not Satisfactory | 0 participants |
| Triple TN 240 mg | Assessment of Tolerability in Triple Combination Therapy | Bad | 0 participants |
| Triple TE 240 mg | Assessment of Tolerability in Triple Combination Therapy | Satisfactory | 0 participants |
| Triple TE 240 mg | Assessment of Tolerability in Triple Combination Therapy | Good | 6 participants |
| Triple TE 240 mg | Assessment of Tolerability in Triple Combination Therapy | Bad | 0 participants |
| Triple TE 240 mg | Assessment of Tolerability in Triple Combination Therapy | Not Satisfactory | 0 participants |
Primary
Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy
Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Time frame: 4 weeks
Population: The treated set (TS) consisted of all patients who were given study medication and were documented to have taken at least one dose of investigational products regardless of randomization randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy | 3 participants |
| Triple TN 120 mg | Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy | 6 participants |
| Triple TN 240 mg | Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy | 6 participants |
| Triple TE 240 mg | Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy | 5 participants |
Primary
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in triple combination therapy for treatment naive patients and treatment experienced patients.
Time frame: 4 weeks
Population: The treated set (TS) consisted of all patients who were given study medication and were documented to have taken at least one dose of investigational products regardless of randomisation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Platelets | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haemoglobin | 3 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Red blood cell ct. | 1 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease White blood cell ct. | 2 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haematocrit | 2 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Eosinophils | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Sodium | 1 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Potassium | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Bicarbonate | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bicarbonate | 1 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, total | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, direct | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Protein, total | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Uric acid | 2 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Triglyceride | 0 participants |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase U. pH | 0 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Eosinophils | 0 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Bicarbonate | 1 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase U. pH | 1 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, direct | 1 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Triglyceride | 0 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bicarbonate | 2 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Red blood cell ct. | 2 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, total | 2 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Platelets | 1 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Sodium | 2 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease White blood cell ct. | 4 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haemoglobin | 3 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Protein, total | 0 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Potassium | 0 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Uric acid | 2 participants |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haematocrit | 2 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Eosinophils | 1 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Platelets | 0 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Uric acid | 0 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Sodium | 2 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Potassium | 1 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase U. pH | 0 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Bicarbonate | 0 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bicarbonate | 1 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Triglyceride | 1 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, total | 6 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, direct | 3 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haematocrit | 3 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haemoglobin | 2 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Protein, total | 1 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Red blood cell ct. | 2 participants |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease White blood cell ct. | 5 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase U. pH | 0 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Potassium | 0 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Red blood cell ct. | 2 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haematocrit | 4 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Uric acid | 1 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Sodium | 1 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Protein, total | 0 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Haemoglobin | 4 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Platelets | 0 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bicarbonate | 2 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Eosinophils | 0 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, total | 5 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Triglyceride | 4 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease Bicarbonate | 1 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Decrease White blood cell ct. | 4 participants |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy | Increase Bilirubin, direct | 4 participants |
Secondary
Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV
An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV.
Time frame: 44 weeks
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Triple TN Placebo | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Good | 2 participant(s) |
| Triple TN Placebo | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Satisfactory | 2 participant(s) |
| Triple TN Placebo | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Not satisfactory | 0 participant(s) |
| Triple TN Placebo | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Bad | 0 participant(s) |
| Triple TN 120 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Satisfactory | 0 participant(s) |
| Triple TN 120 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Not satisfactory | 1 participant(s) |
| Triple TN 120 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Bad | 0 participant(s) |
| Triple TN 120 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Good | 4 participant(s) |
| Triple TN 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Not satisfactory | 1 participant(s) |
| Triple TN 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Satisfactory | 2 participant(s) |
| Triple TN 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Bad | 2 participant(s) |
| Triple TN 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Good | 1 participant(s) |
| Triple TE 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Bad | 0 participant(s) |
| Triple TE 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Satisfactory | 1 participant(s) |
| Triple TE 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Good | 3 participant(s) |
| Triple TE 240 mg | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV | Not satisfactory | 2 participant(s) |
Secondary
AUCτ,1 for BI 201335 ZW
Area under the curve (AUC) concentration after the first dose of BI 201335 ZW
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | AUCτ,1 for BI 201335 ZW | 68900 ng*h/mL | Geometric Coefficient of Variation 25.3 |
| Triple TN 120 mg | AUCτ,1 for BI 201335 ZW | 171000 ng*h/mL | Geometric Coefficient of Variation 21.2 |
| Triple TN 240 mg | AUCτ,1 for BI 201335 ZW | 233000 ng*h/mL | Geometric Coefficient of Variation 38.5 |
Secondary
AUCτ,1 for Ribavirin (RBV)
Area under the plasma concentration curve of RBV after the first dose of placebo or BI 201335 NA with with RBV and PegIFN alfa-2a
Time frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | AUCτ,1 for Ribavirin (RBV) | 5160 ng*h/mL | Geometric Coefficient of Variation 22.1 |
| Triple TN 120 mg | AUCτ,1 for Ribavirin (RBV) | 4660 ng*h/mL | Geometric Coefficient of Variation 35.8 |
| Triple TN 240 mg | AUCτ,1 for Ribavirin (RBV) | 4620 ng*h/mL | Geometric Coefficient of Variation 22.9 |
| Triple TE 240 mg | AUCτ,1 for Ribavirin (RBV) | 3500 ng*h/mL | Geometric Coefficient of Variation 41.2 |
Secondary
AUCτ,ss of BI 201335 ZW
AUC at steady state after 4 weeks combination of the last dose
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | AUCτ,ss of BI 201335 ZW | 70800 ng*h/mL | Geometric Coefficient of Variation 86.5 |
| Triple TN 120 mg | AUCτ,ss of BI 201335 ZW | 361000 ng*h/mL | Geometric Coefficient of Variation 68 |
| Triple TN 240 mg | AUCτ,ss of BI 201335 ZW | 499000 ng*h/mL | Geometric Coefficient of Variation 41.3 |
Secondary
AUCτ,ss of RBV
Area under the plasma concentration curve of RBV after the multiple oral administration of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Time frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | AUCτ,ss of RBV | 27500 ng*h/mL | Geometric Coefficient of Variation 29.5 |
| Triple TN 120 mg | AUCτ,ss of RBV | 25200 ng*h/mL | Geometric Coefficient of Variation 42.4 |
| Triple TN 240 mg | AUCτ,ss of RBV | 22400 ng*h/mL | Geometric Coefficient of Variation 38.5 |
| Triple TE 240 mg | AUCτ,ss of RBV | 20000 ng*h/mL | Geometric Coefficient of Variation 18.7 |
Secondary
Cavg for BI 201335 ZW
average plasma concentration (Cavg) of BI 201335 ZW
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cavg for BI 201335 ZW | 2950 ng/mL | Geometric Coefficient of Variation 86.5 |
| Triple TN 120 mg | Cavg for BI 201335 ZW | 15000 ng/mL | Geometric Coefficient of Variation 68 |
| Triple TN 240 mg | Cavg for BI 201335 ZW | 20800 ng/mL | Geometric Coefficient of Variation 41.3 |
Secondary
Cavg for RBV
average plasma concentration (Cavg) of RBV
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cavg for RBV | 2290 ng/mL | Geometric Coefficient of Variation 29.5 |
| Triple TN 120 mg | Cavg for RBV | 2100 ng/mL | Geometric Coefficient of Variation 42.4 |
| Triple TN 240 mg | Cavg for RBV | 1860 ng/mL | Geometric Coefficient of Variation 38.5 |
| Triple TE 240 mg | Cavg for RBV | 1670 ng/mL | Geometric Coefficient of Variation 18.7 |
Secondary
Change From Baseline in HCV Viral Load
Change form baseline in HCV viral load (log10) after 4 weeks
Time frame: baseline and week 4
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Change From Baseline in HCV Viral Load | -3.30 IU/mL | Standard Error 0.74 |
| Triple TN 120 mg | Change From Baseline in HCV Viral Load | -5.88 IU/mL | Standard Error 0.17 |
| Triple TN 240 mg | Change From Baseline in HCV Viral Load | -5.95 IU/mL | Standard Error 0.21 |
| Triple TE 240 mg | Change From Baseline in HCV Viral Load | -5.53 IU/mL | Standard Error 0.29 |
Secondary
CL/F,ss for BI 201335 ZW
apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | CL/F,ss for BI 201335 ZW | 28.2 mL/min | Geometric Coefficient of Variation 86.5 |
| Triple TN 120 mg | CL/F,ss for BI 201335 ZW | 11.1 mL/min | Geometric Coefficient of Variation 68 |
| Triple TN 240 mg | CL/F,ss for BI 201335 ZW | 8.01 mL/min | Geometric Coefficient of Variation 41.3 |
Secondary
Cmax of BI 201335 ZW
Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cmax of BI 201335 ZW | 5500 ng/mL | Geometric Coefficient of Variation 24.4 |
| Triple TN 120 mg | Cmax of BI 201335 ZW | 12600 ng/mL | Geometric Coefficient of Variation 29 |
| Triple TN 240 mg | Cmax of BI 201335 ZW | 15000 ng/mL | Geometric Coefficient of Variation 40 |
Secondary
Cmax of RBV
Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a
Time frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cmax of RBV | 1130 ng/mL | Geometric Coefficient of Variation 24.9 |
| Triple TN 120 mg | Cmax of RBV | 761 ng/mL | Geometric Coefficient of Variation 29.7 |
| Triple TN 240 mg | Cmax of RBV | 724 ng/mL | Geometric Coefficient of Variation 33.7 |
| Triple TE 240 mg | Cmax of RBV | 509 ng/mL | Geometric Coefficient of Variation 51 |
Secondary
Cmax,ss of BI 201335 ZW
Maximum concentration of BI 201335 ZW at steady state
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cmax,ss of BI 201335 ZW | 5880 ng/mL | Geometric Coefficient of Variation 61.5 |
| Triple TN 120 mg | Cmax,ss of BI 201335 ZW | 24500 ng/mL | Geometric Coefficient of Variation 52.2 |
| Triple TN 240 mg | Cmax,ss of BI 201335 ZW | 29100 ng/mL | Geometric Coefficient of Variation 35.3 |
Secondary
Cmax,ss of RBV
Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Time frame: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose
Population: The pharmacokinetic analysis set (PKS) consisted of all randomised patients who took at least one dose of investigational products and with at least one on treatment blood sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cmax,ss of RBV | 3060 ng/mL | Geometric Coefficient of Variation 35.4 |
| Triple TN 120 mg | Cmax,ss of RBV | 2710 ng/mL | Geometric Coefficient of Variation 47.3 |
| Triple TN 240 mg | Cmax,ss of RBV | 2280 ng/mL | Geometric Coefficient of Variation 43.2 |
| Triple TE 240 mg | Cmax,ss of RBV | 2130 ng/mL | Geometric Coefficient of Variation 18 |
Secondary
Cmin,ss for BI 201335 ZW
Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cmin,ss for BI 201335 ZW | 1550 ng/mL | Geometric Coefficient of Variation 138 |
| Triple TN 120 mg | Cmin,ss for BI 201335 ZW | 10200 ng/mL | Geometric Coefficient of Variation 85 |
| Triple TN 240 mg | Cmin,ss for BI 201335 ZW | 16000 ng/mL | Geometric Coefficient of Variation 54.1 |
Secondary
Cmin,ss for RBV
Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | Cmin,ss for RBV | 1980 ng/mL | Geometric Coefficient of Variation 24.6 |
| Triple TN 120 mg | Cmin,ss for RBV | 1730 ng/mL | Geometric Coefficient of Variation 44 |
| Triple TN 240 mg | Cmin,ss for RBV | 1590 ng/mL | Geometric Coefficient of Variation 36.4 |
| Triple TE 240 mg | Cmin,ss for RBV | 1400 ng/mL | Geometric Coefficient of Variation 18.5 |
Secondary
Complete Early Virological Response (cEVR)
Number of patients with plasma HCV RNA level BLD at Week 12
Time frame: 12 weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Complete Early Virological Response (cEVR) | 3 participants |
| Triple TN 120 mg | Complete Early Virological Response (cEVR) | 5 participants |
| Triple TN 240 mg | Complete Early Virological Response (cEVR) | 5 participants |
| Triple TE 240 mg | Complete Early Virological Response (cEVR) | 6 participants |
Secondary
Day 28 Virologic Response
Number of patients with HCV viral load reduction \>= 2 log10 at Week 4
Time frame: 4 weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Day 28 Virologic Response | 3 participants |
| Triple TN 120 mg | Day 28 Virologic Response | 6 participants |
| Triple TN 240 mg | Day 28 Virologic Response | 6 participants |
| Triple TE 240 mg | Day 28 Virologic Response | 6 participants |
Secondary
Early Virological Response (EVR)
Number of patients with reduction \>= 2 log10 in plasma HCV RNA level at Week 12
Time frame: 12 Weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Early Virological Response (EVR) | 4 participants |
| Triple TN 120 mg | Early Virological Response (EVR) | 5 participants |
| Triple TN 240 mg | Early Virological Response (EVR) | 6 participants |
| Triple TE 240 mg | Early Virological Response (EVR) | 6 participants |
Secondary
End of Treatment Response (ETR)
Number of patients with plasma HCV RNA level BLD at week 48
Time frame: 48 weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | End of Treatment Response (ETR) | 3 participants |
| Triple TN 120 mg | End of Treatment Response (ETR) | 5 participants |
| Triple TN 240 mg | End of Treatment Response (ETR) | 4 participants |
| Triple TE 240 mg | End of Treatment Response (ETR) | 4 participants |
Secondary
Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV
Drug-related AEs in SOC treatment period were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Time frame: 44 weeks
Population: The treated set (TS) consisted of all patients who were given study medication and were documented to have taken at least one dose of investigational products regardless of randomisation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV | 3 participant(s) |
| Triple TN 120 mg | Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV | 5 participant(s) |
| Triple TN 240 mg | Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV | 4 participant(s) |
| Triple TE 240 mg | Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV | 5 participant(s) |
Secondary
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in SOC period for treatment naive patients and treatment experienced patients.
Time frame: 44 weeks
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase bicarbonate | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease potassium | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease platelets | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase ALT/GPT, SGPT | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease sodium | 1 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase eosinophils | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase U. pH | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haematocrit | 1 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease red blood cell ct. | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase AST/GOT, SGOT | 0 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase triglyceride | 1 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase uric acid | 1 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease white blood cell ct. | 3 participant(s) |
| Triple TN Placebo | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haemoglobin | 4 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase triglyceride | 0 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haematocrit | 3 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haemoglobin | 2 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease red blood cell ct. | 3 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease white blood cell ct. | 5 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease platelets | 1 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase eosinophils | 0 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease sodium | 0 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease potassium | 0 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase bicarbonate | 1 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase uric acid | 0 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase U. pH | 2 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase AST/GOT, SGOT | 1 participant(s) |
| Triple TN 120 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase ALT/GPT, SGPT | 1 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase triglyceride | 0 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase AST/GOT, SGOT | 0 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haemoglobin | 2 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease white blood cell ct. | 5 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase U. pH | 0 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haematocrit | 5 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase uric acid | 0 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease potassium | 1 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase eosinophils | 1 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease red blood cell ct. | 4 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease platelets | 0 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase ALT/GPT, SGPT | 0 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease sodium | 1 participant(s) |
| Triple TN 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase bicarbonate | 0 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease sodium | 0 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease potassium | 0 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase AST/GOT, SGOT | 1 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase bicarbonate | 0 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease red blood cell ct. | 3 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase uric acid | 0 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haemoglobin | 5 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase triglyceride | 2 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase ALT/GPT, SGPT | 1 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase U. pH | 0 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease platelets | 0 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease haematocrit | 4 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Increase eosinophils | 1 participant(s) |
| Triple TE 240 mg | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV | Decrease white blood cell ct. | 3 participant(s) |
Secondary
Rapid Virological Response (RVR)
Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4)
Time frame: 4 weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Rapid Virological Response (RVR) | 0 participants |
| Triple TN 120 mg | Rapid Virological Response (RVR) | 5 participants |
| Triple TN 240 mg | Rapid Virological Response (RVR) | 6 participants |
| Triple TE 240 mg | Rapid Virological Response (RVR) | 4 participants |
Secondary
Sustained Virologic Response (SVR)
Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion
Time frame: 72 weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Sustained Virologic Response (SVR) | 2 participants |
| Triple TN 120 mg | Sustained Virologic Response (SVR) | 4 participants |
| Triple TN 240 mg | Sustained Virologic Response (SVR) | 5 participants |
| Triple TE 240 mg | Sustained Virologic Response (SVR) | 3 participants |
Secondary
t1/2,ss for BI 201335 ZW
terminal half-life of the analyte in plasma at steady state (t1/2,ss)
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Triple TN Placebo | t1/2,ss for BI 201335 ZW | 29.3 hour(s) | Geometric Coefficient of Variation 7.7 |
| Triple TN 120 mg | t1/2,ss for BI 201335 ZW | 21.2 hour(s) | Geometric Coefficient of Variation 9 |
| Triple TN 240 mg | t1/2,ss for BI 201335 ZW | 23.0 hour(s) | Geometric Coefficient of Variation 19.8 |
Secondary
Tmax for BI 201335 ZW
Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triple TN Placebo | Tmax for BI 201335 ZW | 4.98 hour(s) |
| Triple TN 120 mg | Tmax for BI 201335 ZW | 5.50 hour(s) |
| Triple TN 240 mg | Tmax for BI 201335 ZW | 7.97 hour(s) |
Secondary
Tmax for RBV
Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triple TN Placebo | Tmax for RBV | 1.94 hour(s) |
| Triple TN 120 mg | Tmax for RBV | 3.98 hour(s) |
| Triple TN 240 mg | Tmax for RBV | 3.92 hour(s) |
| Triple TE 240 mg | Tmax for RBV | 4.98 hour(s) |
Secondary
Tmax, ss for BI 201335 ZW
Time from last dosing to the maximum plasma concentration (tmax) of BI 201335 ZW after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triple TN Placebo | Tmax, ss for BI 201335 ZW | 3.83 hour(s) |
| Triple TN 120 mg | Tmax, ss for BI 201335 ZW | 2.99 hour(s) |
| Triple TN 240 mg | Tmax, ss for BI 201335 ZW | 3.49 hour(s) |
Secondary
Tmax, ss for RBV
Time to the maximum plasma concentration (tmax) of RBV after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
Time frame: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triple TN Placebo | Tmax, ss for RBV | 2.42 hour(s) |
| Triple TN 120 mg | Tmax, ss for RBV | 2.92 hour(s) |
| Triple TN 240 mg | Tmax, ss for RBV | 2.90 hour(s) |
| Triple TE 240 mg | Tmax, ss for RBV | 3.92 hour(s) |
Secondary
Week 2 Virological Response (W2VR)
Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ))
Time frame: 2 weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Week 2 Virological Response (W2VR) | 0 participants |
| Triple TN 120 mg | Week 2 Virological Response (W2VR) | 5 participants |
| Triple TN 240 mg | Week 2 Virological Response (W2VR) | 6 participants |
| Triple TE 240 mg | Week 2 Virological Response (W2VR) | 3 participants |
Secondary
Week 4 Virological Response (W4VR)
Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ))
Time frame: 4 weeks
Population: The full analysis set (FAS) consisted of all randomised patients who were given investigational products and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple TN Placebo | Week 4 Virological Response (W4VR) | 0 participants |
| Triple TN 120 mg | Week 4 Virological Response (W4VR) | 6 participants |
| Triple TN 240 mg | Week 4 Virological Response (W4VR) | 6 participants |
| Triple TE 240 mg | Week 4 Virological Response (W4VR) | 5 participants |