Hepatitis C, Chronic
Conditions
Brief summary
The objective was to investigate the antiviral effect, safety, and pharmacokinetics of BI 201335 (Faldaprevir), given as a soft gelatine capsule, in patients with hepatitis C virus (HCV) genotype 1 infection. Combination therapy of BI 201335 (Faldaprevir) with pegylated interferon α-2a (PegIFN) and ribavirin (RBV), with or without a 3-day lead-in, was assessed in treatment-naïve (TN) and treatment experienced (TE) patients.
Interventions
DRUGBI 201335 NA 240 mg QD / LI
240mg BI 201335 NA (Faldaprevir) once daily with a 3 days lead-in phase of PegIFN/RB, 24 weeks
DRUGPegIFN/RBV
PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks
DRUGBI 201335 NA 120mg QD / LI
120mg BI 201335 NA (Faldaprevir) once daily, for 24 weeks
DRUGBI 201335 NA 240 mg QD
240mg BI 201335 NA (Faldaprevir) once daily, 24 weeks
DRUGBI 201335 NA 240 mg BID
240mg BI 201335 NA (Faldaprevir) twice, 24 weeks
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
chronic HCV GT1; therapy-naive to IFN, PegIFN, or RBV; HCV VL \>=100,000 IU/mL Liver biopsy within 2 years prior to study enrolment showing necroinflammatory activity or presence of fibrosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 age 18-65 years Females and males with adequate contraception
Exclusion criteria
Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection HIV-1 or HIV-2 positive HBV positive Decompensated liver disease, or history of decompensated liver disease Active or suspected malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse within the past 12 months. Usage of any investigational drug within 30 days prior to enrolment, or 5 half-lives, whichever is longer Known hypersensitivity to any ingredient of the study drugs Condition that is defined as one which in the opinion of the investigator may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study Alpha-fetoprotein value \> 100ng/mL at screening; if \>20ng/mL and \<=100ng/mL, patients can be included if there is no evidence of liver cancer in two congruent imaging studies Total bilirubin \> 1.5x ULN wiht ratio of direct/indirect \>1. ALT or AST levels \> 5x ULN INR prolonged to \>1.5x ULN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | Week 28 | An achieved virological response is defined as the plasma Hepatitis C Virus RiboNucleic Acid (HCV RNA) level below the lower limit of detection (BLD). This data was only collected for patients, who stopped trial participation at Week 24 and did not continue with PegIFN/RBV until Week 48. The lower limit of quantification (BLQ) of this assay was 25 IU/mL and the lower limit of detection (BLD) was 10 IU/mL at the time of the protocol finalisation. During the course of the trial, the manufacturer defined BLD as '\< 25 IU/mL, not detectable' and BLQ as '\< 25 IU/mL, detectable'. |
| Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | Day 155 after the end of all treatment | Virological (VL) response was defined as the plasma HCV RNA level below the lower limit of detection. The first VL measurement that occurred in the time window ≥ Day 155 (from End Of Treatment on) was selected for the determination of SVR24. Therefore, patients with virological load BLD 24 weeks after completion of therapy, who had a rebound after this time point (outside the defined time window of 155 days after end of all treatments) were identified as SVR24 achieved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Virological Response (EVR) | Baseline and Week 12 | Early Virological Response (EVR) is defined as ≥ 2 log 10 reduction in plasma HCV RNA level from baseline at Week 12 |
| Extended Rapid Virological Response (eRVR) | Week 4 and Week 12 | Extended Rapid Virological Response (eRVR) is defined as plasma HCV RNA levels below the lower limit of quantification at Week 4 and below the lower limit of detection at Week 12 |
| Complete Early Virological Response (cEVR) | Week 12 | Complete Early Virological Response (cEVR) is defined as plasma HCV RNA level below the lower limit of detection at Week 12 |
| End of Treatment Response at Week 24 | Week 24 | End of Treatment Response of BI 201335 or placebo (ETR BI 201335/placebo ) is defined as plasma HCV RNA level below the lower limit of detection at Week 24. |
| End of Treatment Response at End of All Therapy | Week 24 or Week 48 | End of Treatment Response (ETR) is defined as plasma HCV RNA level below the lower limit of detection at end of all therapy, i.e. at Week 24 or Week 48 |
| Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | Week 36 or Week 60 | Sustained Virological Response 12 Weeks (SVR12) after completion of all therapy is defined as plasma HCV RNA level below the lower limit of detection at 12 weeks after completion of all therapy, i.e. at Week 36 or 60 |
| Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | On or after day 155 post end of all treatment | Summary of time (i.e Median number of days) to reach a plasma HCV RNA level below limit of detection (BLD) |
| Time to Loss of Virological Response | Week 24 | Time to loss of virological response, defined as the last value below the lower limit of detection in a patient who subsequently had 2 consecutive plasma HCV RNA level measurements ≥100 IU/mL. Patients that did not achieve suppression of plasma HCV RNA levels below the lower limit of detection until Week 24 were defined as having a time to failure of zero. Time is expressed in Median number of days. |
| Virological Rebound | Week 24 or Week 48 | Virological rebound is defined as increase of ≥ 1 log 10 in plasma HCV RNA level from a quantifiable nadir, or to ≥ 250 IU/mL after previous nadir \< 25 IU/mL (detectable), or to ≥ 100 IU/mL after a previous viral load below the lower limit of detection. Note that this is numerical rebound, not requiring confirmation with a re-measurement. |
| Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | Up to Week 24 | Number of patients with Unconfirmed rebound ( ≥ 1log10 increase in HCV mRNA) while on BI201335/placebo + 5 days washout. |
| Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | Week 24 through Week 48 | Number of patients with Unconfirmed rebound (≥ 1log10 increase in HCV mRNA) while on PegIFN/RBV treatment + 5 days washout. |
| Relapse | post-End of treatment (i.e. post 48 weeks) | Relapse was rebound after the viral load at end of all treatment had been below the lower limit of detection, or, if the value at end of all treatment was missing, after both the last value before End of Treatment (EOT) and the first value after End of Treatment were below the lower limit of detection. Patients could experience relapse at any point post-treatment. |
| Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Baseline and Week 24 | Baseline is defined as the last value before the initial drug administration of BI 201335 or placebo. |
| Change From Baseline to Week 24 in Pulse Rate | Baseline and Week 24 | Baseline is defined as the last value before the administration of BI 201335 or placebo. |
| Virological Response at Week 2 | Week 2 | Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 2 (\< 25 IU/ml, detectable or undetectable) |
| Global Assessment of Tolerability | Week 24 | The investigator was to assess the tolerability of trial medication based on adverse events (AEs) and the laboratory evaluation. Tolerability was assessed by the investigator according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'. |
| Change From Baseline to Week 24 in Haemoglobin of the Patients | Baseline and Week 24 | Baseline is defined as the last value before the administration of BI 201335 or placebo. |
| Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | Baseline and Week 24 | Number of patients with normal or high baseline moved to low . |
| Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | Baseline and Week 24 | Baseline is defined as the last value before the administration of BI 201335 or placebo. |
| Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | Baseline and Week 24 | Number of patients with normal or high baseline moved to low . |
| Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | Baseline and Week 24 | Baseline is defined as the last value before the drug administration of BI 201335 or placebo. |
| Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | Baseline and Week 24 | Number of patients with normal or low baseline moved to high . |
| Change From Baseline to Week 24 in Total Bilirubin of the Patients | Baseline and Week 24 | Baseline is defined as the last value before the administration of BI 201335 or placebo. |
| Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | Baseline and Week 24 | Number of patients with normal or low baseline moved to high . |
| Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | Week 8, week 10, week 12, week 24 | C(pre,ss) is defined as pre-dose (trough) concentration of Faldaprevir in plasma at steady state immediately before administration of the next dose. |
| Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | Week 8, week 10, week 12, week 24 | C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose. |
| Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | Week 8, week 10, week 12, week 24 | C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose. |
| Trough Concentration (Cpre,ss) of PegIFN at Steady State | Week 8, week 10, week 12, week 24 | C(pre,ss) is defined as pre-dose (trough) concentration of PegIFN in plasma at steady state immediately before administration of the next dose. |
| Change From Baseline to Week 24 in Weight of the Patients | Baseline and Week 24 | Baseline is defined as the last value before the administration of BI 201335 or placebo. |
| Virological Response at Week 4 | Week 4 | Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 4 (\< 25 IU/ml, detectable or undetectable) |
Countries
Argentina, Australia, Austria, Canada, Czechia, France, Germany, Netherlands, Portugal, Romania, South Korea, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo-TN Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
\[PegIFN/RBV : PegIFN (180 µg/wk) and RBV (1000/1200mg/d)\] | 71 |
| 120 mg QD / LI-TN 120 mg BI 201335 (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in (LI) phase of PegIFN/RBV (i.e. initiation of BI 201335 three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients
\[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)\] | 69 |
| 240 mg QD / LI-TN 240 mg BI 201335 once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
\[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)\] | 143 |
| 240 mg QD-TN 240 mg BI 201335 once daily (QD) combined with PegIFN/RBV for 24 weeks, success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients
\[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)\] | 146 |
| 240 mg QD / LI-TE 240 mg BI 201335 once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-experienced (TE) patients
\[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)\] | 142 |
| 240 mg QD-TE 240 mg BI 201335 once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients
\[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)\] | 76 |
| 240 mg BID / LI-TE 240 mg BI 201335 twice daily (BID) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients
\[PegIFN/RBV: PegIFN (180 µg/wk) and RBV (1000/1200mg/d)\] | 70 |
| Total | 717 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 16 | 8 | 8 | 3 | 16 |
| Overall Study | Lack of Efficacy | 11 | 4 | 5 | 3 | 27 | 15 | 9 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Not treated | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Other than those stated above | 1 | 1 | 3 | 2 | 2 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 3 | 1 | 2 | 1 | 0 |
| Overall Study | Refused to continue trial medication | 1 | 3 | 2 | 2 | 6 | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo-TN | 120 mg QD / LI-TN | 240 mg QD / LI-TN | 240 mg QD-TN | 240 mg QD / LI-TE | 240 mg QD-TE | 240 mg BID / LI-TE | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 10.86 | 46.3 years STANDARD_DEVIATION 10.92 | 44.7 years STANDARD_DEVIATION 10.18 | 46.3 years STANDARD_DEVIATION 10.48 | 48.7 years STANDARD_DEVIATION 9.58 | 49.6 years STANDARD_DEVIATION 8.42 | 50.1 years STANDARD_DEVIATION 8.34 | 47.14 years STANDARD_DEVIATION 9.91 |
| Sex: Female, Male Female | 30 Participants | 29 Participants | 69 Participants | 67 Participants | 41 Participants | 26 Participants | 29 Participants | 291 Participants |
| Sex: Female, Male Male | 41 Participants | 40 Participants | 74 Participants | 79 Participants | 101 Participants | 50 Participants | 41 Participants | 426 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 65 / 71 | 65 / 68 | 135 / 138 | 143 / 149 | 135 / 141 | 74 / 76 | 68 / 69 |
| serious Total, serious adverse events | 2 / 71 | 3 / 68 | 18 / 138 | 12 / 149 | 10 / 141 | 5 / 76 | 13 / 69 |
Outcome results
Primary
Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy
Virological (VL) response was defined as the plasma HCV RNA level below the lower limit of detection. The first VL measurement that occurred in the time window ≥ Day 155 (from End Of Treatment on) was selected for the determination of SVR24. Therefore, patients with virological load BLD 24 weeks after completion of therapy, who had a rebound after this time point (outside the defined time window of 155 days after end of all treatments) were identified as SVR24 achieved.
Time frame: Day 155 after the end of all treatment
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | 56.3 percentage of patients |
| 120 mg QD / LI-TN | Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | 72.5 percentage of patients |
| 240 mg QD / LI-TN | Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | 72.3 percentage of patients |
| 240 mg QD-TN | Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | 83.8 percentage of patients |
| 240 mg QD / LI-TE | Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | 28.2 percentage of patients |
| 240 mg QD-TE | Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | 40.8 percentage of patients |
| 240 mg BID / LI-TE | Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy | 31.4 percentage of patients |
p-value: 0.0537Fisher Exact
p-value: 0.0213Fisher Exact
p-value: <0.0001Fisher Exact
p-value: <0.0001Fisher Exact
p-value: <0.0001Fisher Exact
p-value: <0.0001Fisher Exact
Primary
Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo
An achieved virological response is defined as the plasma Hepatitis C Virus RiboNucleic Acid (HCV RNA) level below the lower limit of detection (BLD). This data was only collected for patients, who stopped trial participation at Week 24 and did not continue with PegIFN/RBV until Week 48. The lower limit of quantification (BLQ) of this assay was 25 IU/mL and the lower limit of detection (BLD) was 10 IU/mL at the time of the protocol finalisation. During the course of the trial, the manufacturer defined BLD as '\< 25 IU/mL, not detectable' and BLQ as '\< 25 IU/mL, detectable'.
Time frame: Week 28
Population: Per protocol set (PPS): PPS was subset of full analysis set,consisted of all patients without important protocol deviations .~FAS was composed of all randomised patients who took at least 1 dose of study medication.~For this outcome, only patients who were not on PegIFN/RBV treatment 4 weeks after stop of BI 201335 or Placebo were investigated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | 0.0 percentage of patients |
| 120 mg QD / LI-TN | Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | 14.3 percentage of patients |
| 240 mg QD / LI-TN | Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | 59.7 percentage of patients |
| 240 mg QD-TN | Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | 75.0 percentage of patients |
| 240 mg QD / LI-TE | Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | 20.5 percentage of patients |
| 240 mg QD-TE | Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | 3.3 percentage of patients |
| 240 mg BID / LI-TE | Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo | 0.0 percentage of patients |
Secondary
Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing)
Number of patients with Unconfirmed rebound ( ≥ 1log10 increase in HCV mRNA) while on BI201335/placebo + 5 days washout.
Time frame: Up to Week 24
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | 4.2 percentage of patients |
| 120 mg QD / LI-TN | Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | 5.8 percentage of patients |
| 240 mg QD / LI-TN | Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | 5.0 percentage of patients |
| 240 mg QD-TN | Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | 3.5 percentage of patients |
| 240 mg QD / LI-TE | Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | 25.4 percentage of patients |
| 240 mg QD-TE | Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | 28.9 percentage of patients |
| 240 mg BID / LI-TE | Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) | 17.1 percentage of patients |
Secondary
Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing)
Number of patients with Unconfirmed rebound (≥ 1log10 increase in HCV mRNA) while on PegIFN/RBV treatment + 5 days washout.
Time frame: Week 24 through Week 48
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | 4.2 percentage of patients |
| 120 mg QD / LI-TN | Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | 2.9 percentage of patients |
| 240 mg QD / LI-TN | Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | 0.7 percentage of patients |
| 240 mg QD-TN | Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | 0.0 percentage of patients |
| 240 mg QD / LI-TE | Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | 4.9 percentage of patients |
| 240 mg QD-TE | Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | 6.6 percentage of patients |
| 240 mg BID / LI-TE | Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) | 7.1 percentage of patients |
Secondary
Change From Baseline to Week 24 in Absolute Neutrophils of the Patients
Baseline is defined as the last value before the administration of BI 201335 or placebo.
Time frame: Baseline and Week 24
Population: Treated Set (for patients with change from baseline in Absolute Neutrophils at Week 24)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-TN | Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | -2.57 GI/L | Standard Deviation 1.784 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | -1.84 GI/L | Standard Deviation 1.497 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | -1.83 GI/L | Standard Deviation 2.788 |
| 240 mg QD-TN | Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | -2.10 GI/L | Standard Deviation 1.551 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | -1.87 GI/L | Standard Deviation 1.567 |
| 240 mg QD-TE | Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | -1.47 GI/L | Standard Deviation 1.68 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in Absolute Neutrophils of the Patients | -1.84 GI/L | Standard Deviation 1.885 |
Secondary
Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients
Baseline is defined as the last value before the drug administration of BI 201335 or placebo.
Time frame: Baseline and Week 24
Population: Treated Set (for patients with change from baseline in ALT/GPT,SGPT at Week 24)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-TN | Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | -92.0 U/L | Standard Deviation 86.98 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | -67.7 U/L | Standard Deviation 65.95 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | -64.2 U/L | Standard Deviation 80.46 |
| 240 mg QD-TN | Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | -70.2 U/L | Standard Deviation 92.76 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | -50.8 U/L | Standard Deviation 77.43 |
| 240 mg QD-TE | Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | -62.0 U/L | Standard Deviation 68.6 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients | -61.0 U/L | Standard Deviation 80.46 |
Secondary
Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure
Baseline is defined as the last value before the initial drug administration of BI 201335 or placebo.
Time frame: Baseline and Week 24
Population: Treated Set (for patients with change from baseline in Systolic blood pressure and Diastolic blood pressure at Week 24)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | -0.5 mmHg | Standard Deviation 9.11 |
| Placebo-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | -2.6 mmHg | Standard Deviation 11.48 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | 0.8 mmHg | Standard Deviation 12.41 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | -3.8 mmHg | Standard Deviation 15.51 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | -1.4 mmHg | Standard Deviation 10.87 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | -4.6 mmHg | Standard Deviation 14.59 |
| 240 mg QD-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | -1.9 mmHg | Standard Deviation 10.19 |
| 240 mg QD-TN | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | -3.2 mmHg | Standard Deviation 13.63 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | -1.4 mmHg | Standard Deviation 9.34 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | -1.8 mmHg | Standard Deviation 14.21 |
| 240 mg QD-TE | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | -1.8 mmHg | Standard Deviation 10.39 |
| 240 mg QD-TE | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | -3.4 mmHg | Standard Deviation 12.85 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Diastolic Blood Pressure | -5.3 mmHg | Standard Deviation 10.27 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure | Systolic Blood Pressure | -8.0 mmHg | Standard Deviation 14.38 |
Secondary
Change From Baseline to Week 24 in Haemoglobin of the Patients
Baseline is defined as the last value before the administration of BI 201335 or placebo.
Time frame: Baseline and Week 24
Population: Treated Set (for patients with change from baseline in Haemoglobin at Week 24)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-TN | Change From Baseline to Week 24 in Haemoglobin of the Patients | -3.51 g/dL | Standard Deviation 1.526 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in Haemoglobin of the Patients | -3.41 g/dL | Standard Deviation 1.406 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in Haemoglobin of the Patients | -3.41 g/dL | Standard Deviation 1.177 |
| 240 mg QD-TN | Change From Baseline to Week 24 in Haemoglobin of the Patients | -3.43 g/dL | Standard Deviation 1.493 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in Haemoglobin of the Patients | -3.19 g/dL | Standard Deviation 1.447 |
| 240 mg QD-TE | Change From Baseline to Week 24 in Haemoglobin of the Patients | -3.41 g/dL | Standard Deviation 1.285 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in Haemoglobin of the Patients | -3.82 g/dL | Standard Deviation 1.997 |
Secondary
Change From Baseline to Week 24 in Pulse Rate
Baseline is defined as the last value before the administration of BI 201335 or placebo.
Time frame: Baseline and Week 24
Population: Treated Set (for patients with change from baseline in Pulse rate at Week 24)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-TN | Change From Baseline to Week 24 in Pulse Rate | 4.1 bpm | Standard Deviation 10.22 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in Pulse Rate | 3.1 bpm | Standard Deviation 11.37 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in Pulse Rate | 4.1 bpm | Standard Deviation 14.53 |
| 240 mg QD-TN | Change From Baseline to Week 24 in Pulse Rate | 5.3 bpm | Standard Deviation 11.45 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in Pulse Rate | 5.5 bpm | Standard Deviation 11.3 |
| 240 mg QD-TE | Change From Baseline to Week 24 in Pulse Rate | 7.6 bpm | Standard Deviation 10.77 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in Pulse Rate | 3.1 bpm | Standard Deviation 13.46 |
Secondary
Change From Baseline to Week 24 in Total Bilirubin of the Patients
Baseline is defined as the last value before the administration of BI 201335 or placebo.
Time frame: Baseline and Week 24
Population: Treated Set (for patients with change from baseline in Total Bilirubin at Week 24)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-TN | Change From Baseline to Week 24 in Total Bilirubin of the Patients | 0.03 mg/dL | Standard Deviation 0.181 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in Total Bilirubin of the Patients | 0.70 mg/dL | Standard Deviation 0.625 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in Total Bilirubin of the Patients | 1.65 mg/dL | Standard Deviation 1.279 |
| 240 mg QD-TN | Change From Baseline to Week 24 in Total Bilirubin of the Patients | 1.51 mg/dL | Standard Deviation 0.983 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in Total Bilirubin of the Patients | 1.37 mg/dL | Standard Deviation 0.959 |
| 240 mg QD-TE | Change From Baseline to Week 24 in Total Bilirubin of the Patients | 1.09 mg/dL | Standard Deviation 0.996 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in Total Bilirubin of the Patients | 3.04 mg/dL | Standard Deviation 2.203 |
Secondary
Change From Baseline to Week 24 in Weight of the Patients
Baseline is defined as the last value before the administration of BI 201335 or placebo.
Time frame: Baseline and Week 24
Population: Treated Set (for patients with change from baseline in Weight at Week 24)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-TN | Change From Baseline to Week 24 in Weight of the Patients | -3.3 kg | Standard Deviation 3.11 |
| 120 mg QD / LI-TN | Change From Baseline to Week 24 in Weight of the Patients | -3.7 kg | Standard Deviation 3.14 |
| 240 mg QD / LI-TN | Change From Baseline to Week 24 in Weight of the Patients | -4.2 kg | Standard Deviation 3.81 |
| 240 mg QD-TN | Change From Baseline to Week 24 in Weight of the Patients | -4.8 kg | Standard Deviation 5.07 |
| 240 mg QD / LI-TE | Change From Baseline to Week 24 in Weight of the Patients | -3.4 kg | Standard Deviation 3.36 |
| 240 mg QD-TE | Change From Baseline to Week 24 in Weight of the Patients | -4.3 kg | Standard Deviation 3.67 |
| 240 mg BID / LI-TE | Change From Baseline to Week 24 in Weight of the Patients | -4.8 kg | Standard Deviation 4.4 |
Secondary
Complete Early Virological Response (cEVR)
Complete Early Virological Response (cEVR) is defined as plasma HCV RNA level below the lower limit of detection at Week 12
Time frame: Week 12
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Complete Early Virological Response (cEVR) | 42.3 percentage of patients |
| 120 mg QD / LI-TN | Complete Early Virological Response (cEVR) | 87.0 percentage of patients |
| 240 mg QD / LI-TN | Complete Early Virological Response (cEVR) | 84.4 percentage of patients |
| 240 mg QD-TN | Complete Early Virological Response (cEVR) | 93.0 percentage of patients |
| 240 mg QD / LI-TE | Complete Early Virological Response (cEVR) | 58.5 percentage of patients |
| 240 mg QD-TE | Complete Early Virological Response (cEVR) | 59.2 percentage of patients |
| 240 mg BID / LI-TE | Complete Early Virological Response (cEVR) | 52.9 percentage of patients |
Secondary
Early Virological Response (EVR)
Early Virological Response (EVR) is defined as ≥ 2 log 10 reduction in plasma HCV RNA level from baseline at Week 12
Time frame: Baseline and Week 12
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Early Virological Response (EVR) | 84.5 percentage of patients |
| 120 mg QD / LI-TN | Early Virological Response (EVR) | 89.9 percentage of patients |
| 240 mg QD / LI-TN | Early Virological Response (EVR) | 88.7 percentage of patients |
| 240 mg QD-TN | Early Virological Response (EVR) | 93.0 percentage of patients |
| 240 mg QD / LI-TE | Early Virological Response (EVR) | 72.5 percentage of patients |
| 240 mg QD-TE | Early Virological Response (EVR) | 76.3 percentage of patients |
| 240 mg BID / LI-TE | Early Virological Response (EVR) | 62.9 percentage of patients |
Secondary
End of Treatment Response at End of All Therapy
End of Treatment Response (ETR) is defined as plasma HCV RNA level below the lower limit of detection at end of all therapy, i.e. at Week 24 or Week 48
Time frame: Week 24 or Week 48
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | End of Treatment Response at End of All Therapy | 69.0 percentage of patients |
| 120 mg QD / LI-TN | End of Treatment Response at End of All Therapy | 72.5 percentage of patients |
| 240 mg QD / LI-TN | End of Treatment Response at End of All Therapy | 78.0 percentage of patients |
| 240 mg QD-TN | End of Treatment Response at End of All Therapy | 81.7 percentage of patients |
| 240 mg QD / LI-TE | End of Treatment Response at End of All Therapy | 48.6 percentage of patients |
| 240 mg QD-TE | End of Treatment Response at End of All Therapy | 46.1 percentage of patients |
| 240 mg BID / LI-TE | End of Treatment Response at End of All Therapy | 45.7 percentage of patients |
Secondary
End of Treatment Response at Week 24
End of Treatment Response of BI 201335 or placebo (ETR BI 201335/placebo ) is defined as plasma HCV RNA level below the lower limit of detection at Week 24.
Time frame: Week 24
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | End of Treatment Response at Week 24 | 73.2 percentage of patients |
| 120 mg QD / LI-TN | End of Treatment Response at Week 24 | 82.6 percentage of patients |
| 240 mg QD / LI-TN | End of Treatment Response at Week 24 | 77.3 percentage of patients |
| 240 mg QD-TN | End of Treatment Response at Week 24 | 88.0 percentage of patients |
| 240 mg QD / LI-TE | End of Treatment Response at Week 24 | 58.5 percentage of patients |
| 240 mg QD-TE | End of Treatment Response at Week 24 | 52.6 percentage of patients |
| 240 mg BID / LI-TE | End of Treatment Response at Week 24 | 52.9 percentage of patients |
Secondary
Extended Rapid Virological Response (eRVR)
Extended Rapid Virological Response (eRVR) is defined as plasma HCV RNA levels below the lower limit of quantification at Week 4 and below the lower limit of detection at Week 12
Time frame: Week 4 and Week 12
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Extended Rapid Virological Response (eRVR) | 15.5 percentage of patients |
| 120 mg QD / LI-TN | Extended Rapid Virological Response (eRVR) | 85.5 percentage of patients |
| 240 mg QD / LI-TN | Extended Rapid Virological Response (eRVR) | 80.9 percentage of patients |
| 240 mg QD-TN | Extended Rapid Virological Response (eRVR) | 90.8 percentage of patients |
| 240 mg QD / LI-TE | Extended Rapid Virological Response (eRVR) | 52.1 percentage of patients |
| 240 mg QD-TE | Extended Rapid Virological Response (eRVR) | 52.6 percentage of patients |
| 240 mg BID / LI-TE | Extended Rapid Virological Response (eRVR) | 51.4 percentage of patients |
Secondary
Global Assessment of Tolerability
The investigator was to assess the tolerability of trial medication based on adverse events (AEs) and the laboratory evaluation. Tolerability was assessed by the investigator according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'.
Time frame: Week 24
Population: Per protocol set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo-TN | Global Assessment of Tolerability | Missing | 4.2 percentage of patients |
| Placebo-TN | Global Assessment of Tolerability | Not assessable | 1.4 percentage of patients |
| Placebo-TN | Global Assessment of Tolerability | Satisfactory | 33.8 percentage of patients |
| Placebo-TN | Global Assessment of Tolerability | Not satisfactory | 8.5 percentage of patients |
| Placebo-TN | Global Assessment of Tolerability | Bad | 5.6 percentage of patients |
| Placebo-TN | Global Assessment of Tolerability | Good | 46.5 percentage of patients |
| 120 mg QD / LI-TN | Global Assessment of Tolerability | Not satisfactory | 11.6 percentage of patients |
| 120 mg QD / LI-TN | Global Assessment of Tolerability | Not assessable | 2.9 percentage of patients |
| 120 mg QD / LI-TN | Global Assessment of Tolerability | Satisfactory | 36.2 percentage of patients |
| 120 mg QD / LI-TN | Global Assessment of Tolerability | Good | 40.6 percentage of patients |
| 120 mg QD / LI-TN | Global Assessment of Tolerability | Bad | 2.9 percentage of patients |
| 120 mg QD / LI-TN | Global Assessment of Tolerability | Missing | 5.8 percentage of patients |
| 240 mg QD / LI-TN | Global Assessment of Tolerability | Satisfactory | 36.2 percentage of patients |
| 240 mg QD / LI-TN | Global Assessment of Tolerability | Missing | 1.4 percentage of patients |
| 240 mg QD / LI-TN | Global Assessment of Tolerability | Bad | 5.0 percentage of patients |
| 240 mg QD / LI-TN | Global Assessment of Tolerability | Good | 41.1 percentage of patients |
| 240 mg QD / LI-TN | Global Assessment of Tolerability | Not assessable | 4.3 percentage of patients |
| 240 mg QD / LI-TN | Global Assessment of Tolerability | Not satisfactory | 12.1 percentage of patients |
| 240 mg QD-TN | Global Assessment of Tolerability | Bad | 6.3 percentage of patients |
| 240 mg QD-TN | Global Assessment of Tolerability | Not assessable | 0.0 percentage of patients |
| 240 mg QD-TN | Global Assessment of Tolerability | Missing | 2.8 percentage of patients |
| 240 mg QD-TN | Global Assessment of Tolerability | Good | 47.2 percentage of patients |
| 240 mg QD-TN | Global Assessment of Tolerability | Satisfactory | 31.7 percentage of patients |
| 240 mg QD-TN | Global Assessment of Tolerability | Not satisfactory | 12.0 percentage of patients |
| 240 mg QD / LI-TE | Global Assessment of Tolerability | Good | 41.5 percentage of patients |
| 240 mg QD / LI-TE | Global Assessment of Tolerability | Bad | 9.2 percentage of patients |
| 240 mg QD / LI-TE | Global Assessment of Tolerability | Not satisfactory | 13.4 percentage of patients |
| 240 mg QD / LI-TE | Global Assessment of Tolerability | Missing | 1.4 percentage of patients |
| 240 mg QD / LI-TE | Global Assessment of Tolerability | Not assessable | 1.4 percentage of patients |
| 240 mg QD / LI-TE | Global Assessment of Tolerability | Satisfactory | 33.1 percentage of patients |
| 240 mg QD-TE | Global Assessment of Tolerability | Bad | 9.2 percentage of patients |
| 240 mg QD-TE | Global Assessment of Tolerability | Good | 31.6 percentage of patients |
| 240 mg QD-TE | Global Assessment of Tolerability | Not assessable | 0.0 percentage of patients |
| 240 mg QD-TE | Global Assessment of Tolerability | Satisfactory | 40.8 percentage of patients |
| 240 mg QD-TE | Global Assessment of Tolerability | Not satisfactory | 14.5 percentage of patients |
| 240 mg QD-TE | Global Assessment of Tolerability | Missing | 3.9 percentage of patients |
| 240 mg BID / LI-TE | Global Assessment of Tolerability | Not assessable | 0.0 percentage of patients |
| 240 mg BID / LI-TE | Global Assessment of Tolerability | Satisfactory | 37.1 percentage of patients |
| 240 mg BID / LI-TE | Global Assessment of Tolerability | Bad | 20.0 percentage of patients |
| 240 mg BID / LI-TE | Global Assessment of Tolerability | Good | 20.0 percentage of patients |
| 240 mg BID / LI-TE | Global Assessment of Tolerability | Missing | 0.0 percentage of patients |
| 240 mg BID / LI-TE | Global Assessment of Tolerability | Not satisfactory | 22.9 percentage of patients |
Secondary
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils
Number of patients with normal or high baseline moved to low .
Time frame: Baseline and Week 24
Population: Treated Set (for patients with normal or high baseline Absolute Neutrophils)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | 70.6 percentage of patients |
| 120 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | 66.2 percentage of patients |
| 240 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | 47.8 percentage of patients |
| 240 mg QD-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | 45.3 percentage of patients |
| 240 mg QD / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | 50.0 percentage of patients |
| 240 mg QD-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | 54.5 percentage of patients |
| 240 mg BID / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils | 47.4 percentage of patients |
Secondary
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT
Number of patients with normal or low baseline moved to high .
Time frame: Baseline and Week 24
Population: Treated Set (for patients with normal or low baseline ALT/GPT,SGPT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | 0.0 percentage of patients |
| 120 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | 10.0 percentage of patients |
| 240 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | 3.1 percentage of patients |
| 240 mg QD-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | 0.0 percentage of patients |
| 240 mg QD / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | 8.3 percentage of patients |
| 240 mg QD-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | 16.7 percentage of patients |
| 240 mg BID / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT | 20.0 percentage of patients |
Secondary
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin
Number of patients with normal or high baseline moved to low .
Time frame: Baseline and Week 24
Population: Treated Set (for patients with normal or high baseline Haemoglobin)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | 64.3 percentage of patients |
| 120 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | 62.7 percentage of patients |
| 240 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | 51.1 percentage of patients |
| 240 mg QD-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | 53.4 percentage of patients |
| 240 mg QD / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | 45.3 percentage of patients |
| 240 mg QD-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | 63.2 percentage of patients |
| 240 mg BID / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin | 53.7 percentage of patients |
Secondary
Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin
Number of patients with normal or low baseline moved to high .
Time frame: Baseline and Week 24
Population: Treated Set (for patients with normal or low baseline Total Bilirubin)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | 0.0 percentage of patients |
| 120 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | 9.1 percentage of patients |
| 240 mg QD / LI-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | 15.9 percentage of patients |
| 240 mg QD-TN | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | 8.9 percentage of patients |
| 240 mg QD / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | 29.4 percentage of patients |
| 240 mg QD-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | 17.6 percentage of patients |
| 240 mg BID / LI-TE | Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin | 33.8 percentage of patients |
Secondary
Relapse
Relapse was rebound after the viral load at end of all treatment had been below the lower limit of detection, or, if the value at end of all treatment was missing, after both the last value before End of Treatment (EOT) and the first value after End of Treatment were below the lower limit of detection. Patients could experience relapse at any point post-treatment.
Time frame: post-End of treatment (i.e. post 48 weeks)
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Relapse | 15.5 percentage of patients |
| 120 mg QD / LI-TN | Relapse | 7.2 percentage of patients |
| 240 mg QD / LI-TN | Relapse | 10.6 percentage of patients |
| 240 mg QD-TN | Relapse | 7.7 percentage of patients |
| 240 mg QD / LI-TE | Relapse | 26.8 percentage of patients |
| 240 mg QD-TE | Relapse | 11.8 percentage of patients |
| 240 mg BID / LI-TE | Relapse | 20.0 percentage of patients |
Secondary
Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy
Sustained Virological Response 12 Weeks (SVR12) after completion of all therapy is defined as plasma HCV RNA level below the lower limit of detection at 12 weeks after completion of all therapy, i.e. at Week 36 or 60
Time frame: Week 36 or Week 60
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | 50.7 percentage of patients |
| 120 mg QD / LI-TN | Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | 68.1 percentage of patients |
| 240 mg QD / LI-TN | Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | 65.2 percentage of patients |
| 240 mg QD-TN | Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | 74.6 percentage of patients |
| 240 mg QD / LI-TE | Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | 26.1 percentage of patients |
| 240 mg QD-TE | Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | 35.5 percentage of patients |
| 240 mg BID / LI-TE | Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy | 27.1 percentage of patients |
Secondary
Time to Loss of Virological Response
Time to loss of virological response, defined as the last value below the lower limit of detection in a patient who subsequently had 2 consecutive plasma HCV RNA level measurements ≥100 IU/mL. Patients that did not achieve suppression of plasma HCV RNA levels below the lower limit of detection until Week 24 were defined as having a time to failure of zero. Time is expressed in Median number of days.
Time frame: Week 24
Population: Per protocol set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo-TN | Time to Loss of Virological Response | NA Number of days |
| 120 mg QD / LI-TN | Time to Loss of Virological Response | NA Number of days |
| 240 mg QD / LI-TN | Time to Loss of Virological Response | NA Number of days |
| 240 mg QD-TN | Time to Loss of Virological Response | NA Number of days |
| 240 mg QD / LI-TE | Time to Loss of Virological Response | 230 Number of days |
| 240 mg QD-TE | Time to Loss of Virological Response | 370 Number of days |
| 240 mg BID / LI-TE | Time to Loss of Virological Response | 370 Number of days |
Secondary
Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection
Summary of time (i.e Median number of days) to reach a plasma HCV RNA level below limit of detection (BLD)
Time frame: On or after day 155 post end of all treatment
Population: Per protocol set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo-TN | Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | 113 Days |
| 120 mg QD / LI-TN | Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | 29 Days |
| 240 mg QD / LI-TN | Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | 29 Days |
| 240 mg QD-TN | Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | 29 Days |
| 240 mg QD / LI-TE | Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | 56 Days |
| 240 mg QD-TE | Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | 56 Days |
| 240 mg BID / LI-TE | Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection | 29 Days |
Secondary
Trough Concentration (Cpre,ss) of Faldaprevir at Steady State
C(pre,ss) is defined as pre-dose (trough) concentration of Faldaprevir in plasma at steady state immediately before administration of the next dose.
Time frame: Week 8, week 10, week 12, week 24
Population: All evaluable patients were included in the pharmacokinetic analysis. 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 |
|---|---|---|---|---|
| Placebo-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 10(N=54,98,101,94,54,29) | 1220 ng/mL | Geometric Coefficient of Variation 91.3 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 8(N=52,108,116,107,47,32) | 1310 ng/mL | Geometric Coefficient of Variation 81.7 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 12(N=53,113,119,105,56,30) | 1240 ng/mL | Geometric Coefficient of Variation 91.1 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 24(N=47,86,95,78,39,26) | 1170 ng/mL | Geometric Coefficient of Variation 142 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 10(N=54,98,101,94,54,29) | 6530 ng/mL | Geometric Coefficient of Variation 118 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 8(N=52,108,116,107,47,32) | 6550 ng/mL | Geometric Coefficient of Variation 106 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 24(N=47,86,95,78,39,26) | 6440 ng/mL | Geometric Coefficient of Variation 109 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 12(N=53,113,119,105,56,30) | 6380 ng/mL | Geometric Coefficient of Variation 125 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 24(N=47,86,95,78,39,26) | 6610 ng/mL | Geometric Coefficient of Variation 132 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 8(N=52,108,116,107,47,32) | 6190 ng/mL | Geometric Coefficient of Variation 169 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 10(N=54,98,101,94,54,29) | 6340 ng/mL | Geometric Coefficient of Variation 99.7 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 12(N=53,113,119,105,56,30) | 6780 ng/mL | Geometric Coefficient of Variation 100 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 24(N=47,86,95,78,39,26) | 6630 ng/mL | Geometric Coefficient of Variation 102 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 8(N=52,108,116,107,47,32) | 7230 ng/mL | Geometric Coefficient of Variation 94.3 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 12(N=53,113,119,105,56,30) | 6400 ng/mL | Geometric Coefficient of Variation 123 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 10(N=54,98,101,94,54,29) | 6370 ng/mL | Geometric Coefficient of Variation 137 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 10(N=54,98,101,94,54,29) | 7020 ng/mL | Geometric Coefficient of Variation 108 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 8(N=52,108,116,107,47,32) | 6410 ng/mL | Geometric Coefficient of Variation 95.4 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 12(N=53,113,119,105,56,30) | 5980 ng/mL | Geometric Coefficient of Variation 91.2 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 24(N=47,86,95,78,39,26) | 4280 ng/mL | Geometric Coefficient of Variation 179 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 24(N=47,86,95,78,39,26) | 33900 ng/mL | Geometric Coefficient of Variation 509 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 10(N=54,98,101,94,54,29) | 43500 ng/mL | Geometric Coefficient of Variation 72.2 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 12(N=53,113,119,105,56,30) | 46300 ng/mL | Geometric Coefficient of Variation 58.7 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Faldaprevir at Steady State | week 8(N=52,108,116,107,47,32) | 51100 ng/mL | Geometric Coefficient of Variation 55.1 |
Secondary
Trough Concentration (Cpre,ss) of PegIFN at Steady State
C(pre,ss) is defined as pre-dose (trough) concentration of PegIFN in plasma at steady state immediately before administration of the next dose.
Time frame: Week 8, week 10, week 12, week 24
Population: All evaluable patients were included in the pharmacokinetic analysis. 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 |
|---|---|---|---|---|
| Placebo-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 8(N=55,46,80,91,80,36,33) | 14500 ng/mL | Geometric Coefficient of Variation 83.9 |
| Placebo-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 10(N=46,48,88,94,80,40,33) | 14700 ng/mL | Geometric Coefficient of Variation 86.6 |
| Placebo-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 24(N=49,42,74,87,75,40,38) | 17300 ng/mL | Geometric Coefficient of Variation 45.4 |
| Placebo-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 12(N=54,51,100,107,105,56,42) | 15600 ng/mL | Geometric Coefficient of Variation 77.9 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 24(N=49,42,74,87,75,40,38) | 17200 ng/mL | Geometric Coefficient of Variation 83.8 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 8(N=55,46,80,91,80,36,33) | 14800 ng/mL | Geometric Coefficient of Variation 59.9 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 10(N=46,48,88,94,80,40,33) | 13400 ng/mL | Geometric Coefficient of Variation 87.1 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 12(N=54,51,100,107,105,56,42) | 13000 ng/mL | Geometric Coefficient of Variation 102 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 10(N=46,48,88,94,80,40,33) | 14600 ng/mL | Geometric Coefficient of Variation 70.2 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 24(N=49,42,74,87,75,40,38) | 16900 ng/mL | Geometric Coefficient of Variation 42.2 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 8(N=55,46,80,91,80,36,33) | 14900 ng/mL | Geometric Coefficient of Variation 41.1 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 12(N=54,51,100,107,105,56,42) | 13700 ng/mL | Geometric Coefficient of Variation 89.4 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 12(N=54,51,100,107,105,56,42) | 14600 ng/mL | Geometric Coefficient of Variation 70.5 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 8(N=55,46,80,91,80,36,33) | 15100 ng/mL | Geometric Coefficient of Variation 58.5 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 24(N=49,42,74,87,75,40,38) | 16700 ng/mL | Geometric Coefficient of Variation 50.3 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 10(N=46,48,88,94,80,40,33) | 15500 ng/mL | Geometric Coefficient of Variation 52.2 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 24(N=49,42,74,87,75,40,38) | 15600 ng/mL | Geometric Coefficient of Variation 44 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 10(N=46,48,88,94,80,40,33) | 11300 ng/mL | Geometric Coefficient of Variation 144 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 8(N=55,46,80,91,80,36,33) | 11300 ng/mL | Geometric Coefficient of Variation 151 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 12(N=54,51,100,107,105,56,42) | 13100 ng/mL | Geometric Coefficient of Variation 105 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 10(N=46,48,88,94,80,40,33) | 11600 ng/mL | Geometric Coefficient of Variation 155 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 24(N=49,42,74,87,75,40,38) | 15300 ng/mL | Geometric Coefficient of Variation 63.3 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 8(N=55,46,80,91,80,36,33) | 11100 ng/mL | Geometric Coefficient of Variation 125 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 12(N=54,51,100,107,105,56,42) | 13800 ng/mL | Geometric Coefficient of Variation 110 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 12(N=54,51,100,107,105,56,42) | 13500 ng/mL | Geometric Coefficient of Variation 102 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 10(N=46,48,88,94,80,40,33) | 12500 ng/mL | Geometric Coefficient of Variation 85.4 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 8(N=55,46,80,91,80,36,33) | 12300 ng/mL | Geometric Coefficient of Variation 95.1 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of PegIFN at Steady State | week 24(N=49,42,74,87,75,40,38) | 15700 ng/mL | Geometric Coefficient of Variation 38.5 |
Secondary
Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV)
C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose.
Time frame: Week 8, week 10, week 12, week 24
Population: All evaluable patients were included in the pharmacokinetic analysis. 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 |
|---|---|---|---|---|
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 8(N=23,25,46,43,38,20,12) | 2260 ng/mL | Geometric Coefficient of Variation 26.6 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 24(N=21,18,37,34,28,16,11) | 2370 ng/mL | Geometric Coefficient of Variation 34.6 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 12(N=22,27,45,47,37,21,11) | 2200 ng/mL | Geometric Coefficient of Variation 25.1 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 10(N=22,27,50,38,34,25,11) | 2210 ng/mL | Geometric Coefficient of Variation 28.2 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 10(N=22,27,50,38,34,25,11) | 1960 ng/mL | Geometric Coefficient of Variation 33.3 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 8(N=23,25,46,43,38,20,12) | 1920 ng/mL | Geometric Coefficient of Variation 37.9 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 24(N=21,18,37,34,28,16,11) | 2100 ng/mL | Geometric Coefficient of Variation 45.3 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 12(N=22,27,45,47,37,21,11) | 2060 ng/mL | Geometric Coefficient of Variation 35.9 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 8(N=23,25,46,43,38,20,12) | 2320 ng/mL | Geometric Coefficient of Variation 30.8 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 10(N=22,27,50,38,34,25,11) | 2290 ng/mL | Geometric Coefficient of Variation 30.8 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 12(N=22,27,45,47,37,21,11) | 2290 ng/mL | Geometric Coefficient of Variation 33.6 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 24(N=21,18,37,34,28,16,11) | 2390 ng/mL | Geometric Coefficient of Variation 29.6 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 24(N=21,18,37,34,28,16,11) | 2260 ng/mL | Geometric Coefficient of Variation 37.3 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 8(N=23,25,46,43,38,20,12) | 2200 ng/mL | Geometric Coefficient of Variation 28.7 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 10(N=22,27,50,38,34,25,11) | 2330 ng/mL | Geometric Coefficient of Variation 23.8 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 12(N=22,27,45,47,37,21,11) | 2340 ng/mL | Geometric Coefficient of Variation 29.5 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 8(N=23,25,46,43,38,20,12) | 2150 ng/mL | Geometric Coefficient of Variation 26.4 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 10(N=22,27,50,38,34,25,11) | 2190 ng/mL | Geometric Coefficient of Variation 28.9 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 12(N=22,27,45,47,37,21,11) | 2140 ng/mL | Geometric Coefficient of Variation 28.2 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 24(N=21,18,37,34,28,16,11) | 1960 ng/mL | Geometric Coefficient of Variation 35.5 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 12(N=22,27,45,47,37,21,11) | 2150 ng/mL | Geometric Coefficient of Variation 23.6 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 8(N=23,25,46,43,38,20,12) | 2090 ng/mL | Geometric Coefficient of Variation 26 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 10(N=22,27,50,38,34,25,11) | 2140 ng/mL | Geometric Coefficient of Variation 24.6 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 24(N=21,18,37,34,28,16,11) | 2270 ng/mL | Geometric Coefficient of Variation 25 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 12(N=22,27,45,47,37,21,11) | 2300 ng/mL | Geometric Coefficient of Variation 27.3 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 24(N=21,18,37,34,28,16,11) | 1970 ng/mL | Geometric Coefficient of Variation 47.1 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 8(N=23,25,46,43,38,20,12) | 2180 ng/mL | Geometric Coefficient of Variation 27.1 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) | week 10(N=22,27,50,38,34,25,11) | 2300 ng/mL | Geometric Coefficient of Variation 21.5 |
Secondary
Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV)
C(pre,ss) is defined as pre-dose (trough) concentration of Ribavirin in plasma at steady state immediately before administration of the next dose.
Time frame: Week 8, week 10, week 12, week 24
Population: All evaluable patients were included in the pharmacokinetic analysis. 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 |
|---|---|---|---|---|
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 10(N=27,22,43,45,47,22,22) | 1780 ng/mL | Geometric Coefficient of Variation 97.3 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 12(N=27,21,46,47,44,25,22) | 1880 ng/mL | Geometric Coefficient of Variation 59.1 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 8(N=24,21,45,48,49,25,23) | 1670 ng/mL | Geometric Coefficient of Variation 118 |
| Placebo-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 24(N=21,19,33,39,38,18,17) | 2030 ng/mL | Geometric Coefficient of Variation 27 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 8(N=24,21,45,48,49,25,23) | 2010 ng/mL | Geometric Coefficient of Variation 30.4 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 10(N=27,22,43,45,47,22,22) | 1970 ng/mL | Geometric Coefficient of Variation 28.5 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 24(N=21,19,33,39,38,18,17) | 2390 ng/mL | Geometric Coefficient of Variation 23.3 |
| 120 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 12(N=27,21,46,47,44,25,22) | 1900 ng/mL | Geometric Coefficient of Variation 37 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 8(N=24,21,45,48,49,25,23) | 2060 ng/mL | Geometric Coefficient of Variation 26.5 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 24(N=21,19,33,39,38,18,17) | 1970 ng/mL | Geometric Coefficient of Variation 32.2 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 12(N=27,21,46,47,44,25,22) | 2090 ng/mL | Geometric Coefficient of Variation 21.7 |
| 240 mg QD / LI-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 10(N=27,22,43,45,47,22,22) | 2100 ng/mL | Geometric Coefficient of Variation 26.1 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 12(N=27,21,46,47,44,25,22) | 2260 ng/mL | Geometric Coefficient of Variation 26 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 24(N=21,19,33,39,38,18,17) | 2250 ng/mL | Geometric Coefficient of Variation 23 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 10(N=27,22,43,45,47,22,22) | 2280 ng/mL | Geometric Coefficient of Variation 26.5 |
| 240 mg QD-TN | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 8(N=24,21,45,48,49,25,23) | 2170 ng/mL | Geometric Coefficient of Variation 30.4 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 8(N=24,21,45,48,49,25,23) | 2060 ng/mL | Geometric Coefficient of Variation 30.5 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 10(N=27,22,43,45,47,22,22) | 2090 ng/mL | Geometric Coefficient of Variation 30.5 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 12(N=27,21,46,47,44,25,22) | 2190 ng/mL | Geometric Coefficient of Variation 29 |
| 240 mg QD / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 24(N=21,19,33,39,38,18,17) | 2180 ng/mL | Geometric Coefficient of Variation 27.7 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 10(N=27,22,43,45,47,22,22) | 1980 ng/mL | Geometric Coefficient of Variation 35.3 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 24(N=21,19,33,39,38,18,17) | 2050 ng/mL | Geometric Coefficient of Variation 31.9 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 12(N=27,21,46,47,44,25,22) | 2010 ng/mL | Geometric Coefficient of Variation 33.2 |
| 240 mg QD-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 8(N=24,21,45,48,49,25,23) | 2170 ng/mL | Geometric Coefficient of Variation 40.2 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 8(N=24,21,45,48,49,25,23) | 1880 ng/mL | Geometric Coefficient of Variation 37.2 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 12(N=27,21,46,47,44,25,22) | 1950 ng/mL | Geometric Coefficient of Variation 24.9 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 24(N=21,19,33,39,38,18,17) | 2220 ng/mL | Geometric Coefficient of Variation 29.7 |
| 240 mg BID / LI-TE | Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) | week 10(N=27,22,43,45,47,22,22) | 2090 ng/mL | Geometric Coefficient of Variation 34.4 |
Secondary
Virological Rebound
Virological rebound is defined as increase of ≥ 1 log 10 in plasma HCV RNA level from a quantifiable nadir, or to ≥ 250 IU/mL after previous nadir \< 25 IU/mL (detectable), or to ≥ 100 IU/mL after a previous viral load below the lower limit of detection. Note that this is numerical rebound, not requiring confirmation with a re-measurement.
Time frame: Week 24 or Week 48
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Virological Rebound | 28.2 percentage of patients |
| 120 mg QD / LI-TN | Virological Rebound | 17.4 percentage of patients |
| 240 mg QD / LI-TN | Virological Rebound | 19.9 percentage of patients |
| 240 mg QD-TN | Virological Rebound | 12.0 percentage of patients |
| 240 mg QD / LI-TE | Virological Rebound | 67.6 percentage of patients |
| 240 mg QD-TE | Virological Rebound | 53.9 percentage of patients |
| 240 mg BID / LI-TE | Virological Rebound | 60.0 percentage of patients |
Secondary
Virological Response at Week 2
Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 2 (\< 25 IU/ml, detectable or undetectable)
Time frame: Week 2
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Virological Response at Week 2 | 1.4 percentage of patients |
| 120 mg QD / LI-TN | Virological Response at Week 2 | 69.6 percentage of patients |
| 240 mg QD / LI-TN | Virological Response at Week 2 | 66.7 percentage of patients |
| 240 mg QD-TN | Virological Response at Week 2 | 82.4 percentage of patients |
| 240 mg QD / LI-TE | Virological Response at Week 2 | 27.5 percentage of patients |
| 240 mg QD-TE | Virological Response at Week 2 | 34.2 percentage of patients |
| 240 mg BID / LI-TE | Virological Response at Week 2 | 47.1 percentage of patients |
Secondary
Virological Response at Week 4
Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 4 (\< 25 IU/ml, detectable or undetectable)
Time frame: Week 4
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-TN | Virological Response at Week 4 | 16.9 percentage of patients |
| 120 mg QD / LI-TN | Virological Response at Week 4 | 89.9 percentage of patients |
| 240 mg QD / LI-TN | Virological Response at Week 4 | 86.5 percentage of patients |
| 240 mg QD-TN | Virological Response at Week 4 | 93.7 percentage of patients |
| 240 mg QD / LI-TE | Virological Response at Week 4 | 63.4 percentage of patients |
| 240 mg QD-TE | Virological Response at Week 4 | 60.5 percentage of patients |
| 240 mg BID / LI-TE | Virological Response at Week 4 | 68.6 percentage of patients |