Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)
Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo |
0.0; 14.3; 59.7; 75.0; 20.5; 3.3 | — |
| PRIMARY Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy |
56.3; 72.5; 72.3; 83.8; 28.2; 40.8 | 0.0537 |
| SECONDARY Virological Response at Week 2 |
1.4; 69.6; 66.7; 82.4; 27.5; 34.2 | — |
| SECONDARY Virological Response at Week 4 |
16.9; 89.9; 86.5; 93.7; 63.4; 60.5 | — |
| SECONDARY Early Virological Response (EVR) |
84.5; 89.9; 88.7; 93.0; 72.5; 76.3 | — |
| SECONDARY Extended Rapid Virological Response (eRVR) |
15.5; 85.5; 80.9; 90.8; 52.1; 52.6 | — |
| SECONDARY Complete Early Virological Response (cEVR) |
42.3; 87.0; 84.4; 93.0; 58.5; 59.2 | — |
| SECONDARY End of Treatment Response at Week 24 |
73.2; 82.6; 77.3; 88.0; 58.5; 52.6 | — |
| SECONDARY End of Treatment Response at End of All Therapy |
69.0; 72.5; 78.0; 81.7; 48.6; 46.1 | — |
| SECONDARY Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy |
50.7; 68.1; 65.2; 74.6; 26.1; 35.5 | — |
| SECONDARY Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection |
113; 29; 29; 29; 56; 56 | — |
| SECONDARY Time to Loss of Virological Response |
NA; NA; NA; NA; 230; 370 | — |
| SECONDARY Virological Rebound |
28.2; 17.4; 19.9; 12.0; 67.6; 53.9 | — |
| SECONDARY Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing) |
4.2; 5.8; 5.0; 3.5; 25.4; 28.9 | — |
| SECONDARY Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing) |
4.2; 2.9; 0.7; 0.0; 4.9; 6.6 | — |
| SECONDARY Relapse |
15.5; 7.2; 10.6; 7.7; 26.8; 11.8 | — |
| SECONDARY Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure |
-0.5; 0.8; -1.4; -1.9; -1.4; -1.8 | — |
| SECONDARY Change From Baseline to Week 24 in Pulse Rate |
4.1; 3.1; 4.1; 5.3; 5.5; 7.6 | — |
| SECONDARY Change From Baseline to Week 24 in Weight of the Patients |
-3.3; -3.7; -4.2; -4.8; -3.4; -4.3 | — |
| SECONDARY Global Assessment of Tolerability |
46.5; 40.6; 41.1; 47.2; 41.5; 31.6 | — |
| SECONDARY Change From Baseline to Week 24 in Haemoglobin of the Patients |
-3.51; -3.41; -3.41; -3.43; -3.19; -3.41 | — |
| SECONDARY Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin |
64.3; 62.7; 51.1; 53.4; 45.3; 63.2 | — |
| SECONDARY Change From Baseline to Week 24 in Absolute Neutrophils of the Patients |
-2.57; -1.84; -1.83; -2.10; -1.87; -1.47 | — |
| SECONDARY Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils |
70.6; 66.2; 47.8; 45.3; 50.0; 54.5 | — |
| SECONDARY Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients |
-92.0; -67.7; -64.2; -70.2; -50.8; -62.0 | — |
| SECONDARY Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT |
0.0; 10.0; 3.1; 0.0; 8.3; 16.7 | — |
| SECONDARY Change From Baseline to Week 24 in Total Bilirubin of the Patients |
0.03; 0.70; 1.65; 1.51; 1.37; 1.09 | — |
| SECONDARY Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin |
0.0; 9.1; 15.9; 8.9; 29.4; 17.6 | — |
| SECONDARY Trough Concentration (Cpre,ss) of Faldaprevir at Steady State |
1310; 6550; 6190; 7230; 6410; 51100 | — |
| SECONDARY Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV) |
2260; 1920; 2320; 2200; 2150; 2090 | — |
| SECONDARY Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV) |
1670; 2010; 2060; 2170; 2060; 2170 | — |
| SECONDARY Trough Concentration (Cpre,ss) of PegIFN at Steady State |
14500; 14800; 14900; 15100; 11300; 11100 | — |
Eligibility Criteria
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 1.5x ULN wiht ratio of direct/indirect >1. ALT or AST levels > 5x ULN INR prolonged to >1.5x ULN Exclusion criteria related to PegIFN and/or RBV restrictions.
Data sourced from ClinicalTrials.gov (NCT00774397). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.