Tuesday, March 16, 2010 12:39:46 PM
SILEN-C2: EARLY ANTIVIRAL ACTIVITY AND SAFETY OF BI 201335 COMBINED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN (PEGIFN/RBV) IN CHRONIC HCV GENOTYPE-1 PATIENTS WITH NON-RESPONSE TO PEGIFN/RBV
http://www.kenes.com/easl2010/Orals/298.htm
M. Sulkowski1, M. Bourliere2, J.-P. Bronowicki3, A. Streinu-Cercel4, L. Preotescu4, T. Asselah5, J.-M. Pawlotsky6, S. Shafran7, S. Pol8, F.A. Caruntu4, S. Mauss9, D. Larrey10, C. Häfner11, Y. Datsenko11, J. Stern12, R. Kubiak11, G. Steinmann11
1Department of Viral Hepatitis, Johns Hopkins University, Baltimore, MD, USA, 2Hôpital Saint Joseph, Marseille, 3Hôpital de Brabois, Vandoeuvre Cedex, France, 4'Prof. Dr. Matei Bals' Institute of Infectious Diseases 1, Bucharest, Romania, 5Hôpital Beaujon, Clichy Cedex, 6Hôpital Henri Mondor, Créteil, France, 7University of Alberta, Edmonton, AB, Canada, 8Hôpital Cochin, Paris, France, 9Center for HIV and Hepatogastroenterology, Düsseldorf, Germany, 10Hôpital Saint-Eloi, Montpellier Cedex, France, 11Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/ Riß, Germany, 12Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA. *msulkowski@jhmi.edu
Background and aims: BI 201335 is a potent HCV NS3/4A protease inhibitor being studied in phase IIb trials of chronic HCV genotype-1 (GT1) infection.
Methods: In a double-blind, randomized, parallel group design, HCV GT1 patients with confirmed non-response to at least 12 wks of PegIFN/RBV treatment were randomized 1:2:1 to (1) 240 mg BI 201335 once daily (QD), (2) 240 mg BI 201335 QD after a 3 day lead-in phase (LI) of PegIFN/RBV, and (3) 240 mg BI 201335 twice daily (BID) after a 3 day LI. Relapsers and patients with liver cirrhosis were excluded. In each group, treatment is for 24 wks with a background of PegIFN (180 µg/wk) and RBV (1000/1200mg/d). Pre-specified Interim analysis after 12 weeks of therapy is reported. Viral rebound is defined as an increase in plasma HCV RNA = 1 log10 on-treatment from nadir or confirmed increase = 100 IU/ml if previously undetectable.
Results: 288 patients were treated (mean age 49 +/- 9 years; mean BMI 26.4 +/- 4.4 kg/m2; mean log10 HCV RNA at baseline 6.6 IU/mL). BI 201335 with PegIFN/RBV was overall well tolerated and demonstrated potent antiviral activity in all dose groups (Table). Mean ALT improved in all groups. 8% of patients prematurely discontinued treatment due to adverse events (AE). Most frequent AE were gastrointestinal disorders, mostly mild jaundice resulting from isolated unconjugated hyperbilirubinemia, (9.2%, 14.1% and 34.3% in groups 1, 2 and 3) and mostly mild to moderate rash or photosensitivity reactions (severe rash in 1.3, 0.7 and 5.7% in groups 1, 2 and 3).
http://www.kenes.com/easl2010/Orals/298.htm
M. Sulkowski1, M. Bourliere2, J.-P. Bronowicki3, A. Streinu-Cercel4, L. Preotescu4, T. Asselah5, J.-M. Pawlotsky6, S. Shafran7, S. Pol8, F.A. Caruntu4, S. Mauss9, D. Larrey10, C. Häfner11, Y. Datsenko11, J. Stern12, R. Kubiak11, G. Steinmann11
1Department of Viral Hepatitis, Johns Hopkins University, Baltimore, MD, USA, 2Hôpital Saint Joseph, Marseille, 3Hôpital de Brabois, Vandoeuvre Cedex, France, 4'Prof. Dr. Matei Bals' Institute of Infectious Diseases 1, Bucharest, Romania, 5Hôpital Beaujon, Clichy Cedex, 6Hôpital Henri Mondor, Créteil, France, 7University of Alberta, Edmonton, AB, Canada, 8Hôpital Cochin, Paris, France, 9Center for HIV and Hepatogastroenterology, Düsseldorf, Germany, 10Hôpital Saint-Eloi, Montpellier Cedex, France, 11Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/ Riß, Germany, 12Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA. *msulkowski@jhmi.edu
Background and aims: BI 201335 is a potent HCV NS3/4A protease inhibitor being studied in phase IIb trials of chronic HCV genotype-1 (GT1) infection.
Methods: In a double-blind, randomized, parallel group design, HCV GT1 patients with confirmed non-response to at least 12 wks of PegIFN/RBV treatment were randomized 1:2:1 to (1) 240 mg BI 201335 once daily (QD), (2) 240 mg BI 201335 QD after a 3 day lead-in phase (LI) of PegIFN/RBV, and (3) 240 mg BI 201335 twice daily (BID) after a 3 day LI. Relapsers and patients with liver cirrhosis were excluded. In each group, treatment is for 24 wks with a background of PegIFN (180 µg/wk) and RBV (1000/1200mg/d). Pre-specified Interim analysis after 12 weeks of therapy is reported. Viral rebound is defined as an increase in plasma HCV RNA = 1 log10 on-treatment from nadir or confirmed increase = 100 IU/ml if previously undetectable.
Results: 288 patients were treated (mean age 49 +/- 9 years; mean BMI 26.4 +/- 4.4 kg/m2; mean log10 HCV RNA at baseline 6.6 IU/mL). BI 201335 with PegIFN/RBV was overall well tolerated and demonstrated potent antiviral activity in all dose groups (Table). Mean ALT improved in all groups. 8% of patients prematurely discontinued treatment due to adverse events (AE). Most frequent AE were gastrointestinal disorders, mostly mild jaundice resulting from isolated unconjugated hyperbilirubinemia, (9.2%, 14.1% and 34.3% in groups 1, 2 and 3) and mostly mild to moderate rash or photosensitivity reactions (severe rash in 1.3, 0.7 and 5.7% in groups 1, 2 and 3).
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