PMID- 22414766
OWN - NLM
STAT- MEDLINE
DCOM- 20121105
LR  - 20220110
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 57
IP  - 1
DP  - 2012 Jul
TI  - Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase 
      inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin.
PG  - 39-46
LID - 10.1016/j.jhep.2012.02.015 [doi]
AB  - BACKGROUND & AIMS: BI 207127 is a potent non-nucleoside hepatitis C virus (HCV) 
      NS5B polymerase inhibitor in vitro. METHODS: In this double-blind, 
      placebo-controlled study, 57 HCV genotype (GT)-1 patients (n=27 treatment-naive 
      [TN]; n=30 treatment-experienced [TE]) with compensated liver disease were 
      randomised for 28-day treatment with 400, 600, or 800 mg BI 207127 three times 
      daily (TID) or placebo (only TN) in combination with peginterferon alfa 2a and 
      ribavirin (PegIFN/RBV). Plasma HCV RNA was measured by Roche COBAS TaqMan assay. 
      RESULTS: HCV RNA decreased in a dose-dependent manner with little difference 
      between 600 mg (TN 5.6 log(10), TE 4.2 log(10)) and 800 mg (TN 5.4 log(10), TE 
      4.5 log(10)). Rapid virological response (RVR; HCV RNA <15 IU/ml) at day 28 
      occurred in 11/19 TN and 4/30 TE patients treated with BI 207127. GT-1b patients 
      had stronger reductions in HCV RNA than GT-1a (RVR: TN 64% vs. 43%; TE 33% vs. 
      5%). There were no breakthroughs (HCV RNA rebound >1 log(10) from nadir) in the 
      TN groups, whereas 3/30 TE patients experienced breakthrough due to 
      P495-mutations. Gastrointestinal adverse events (AEs) and rash were the major AEs 
      and most frequent at higher doses. One and four patients discontinued due to AEs 
      in the 600 and 800 mg groups, respectively. Overall, tolerability was good and 
      better at 600 mg than 800 mg. CONCLUSIONS: BI 207127 in combination with 
      PegIFN/RBV demonstrated strong antiviral activity with a favourable safety and 
      tolerability profile. The best benefit/risk ratio was observed at 600 mg.
CI  - Copyright (c) 2012 European Association for the Study of the Liver. Published by 
      Elsevier B.V. All rights reserved.
FAU - Larrey, Dominique
AU  - Larrey D
AD  - Servise d'Hepato-Gastro-Enterologie et Transplantation, Hopital Saint Eloi, 80 
      Avenue Augustin Fliche, 34295 Montepellier, France. dom-larrey@chu-montpellier.fr
FAU - Lohse, Ansgar W
AU  - Lohse AW
FAU - de Ledinghen, Victor
AU  - de Ledinghen V
FAU - Trepo, Christian
AU  - Trepo C
FAU - Gerlach, Tilman
AU  - Gerlach T
FAU - Zarski, Jean-Pierre
AU  - Zarski JP
FAU - Tran, Albert
AU  - Tran A
FAU - Mathurin, Philippe
AU  - Mathurin P
FAU - Thimme, Robert
AU  - Thimme R
FAU - Arasteh, Keikawus
AU  - Arasteh K
FAU - Trautwein, Christian
AU  - Trautwein C
FAU - Cerny, Andreas
AU  - Cerny A
FAU - Dikopoulos, Nektarios
AU  - Dikopoulos N
FAU - Schuchmann, Marcus
AU  - Schuchmann M
FAU - Heim, Markus H
AU  - Heim MH
FAU - Gerken, Guido
AU  - Gerken G
FAU - Stern, Jerry O
AU  - Stern JO
FAU - Wu, Katherine
AU  - Wu K
FAU - Abdallah, Nasri
AU  - Abdallah N
FAU - Girlich, Birgit
AU  - Girlich B
FAU - Scherer, Joseph
AU  - Scherer J
FAU - Berger, Frank
AU  - Berger F
FAU - Marquis, Martin
AU  - Marquis M
FAU - Kukolj, George
AU  - Kukolj G
FAU - Bocher, Wulf
AU  - Bocher W
FAU - Steffgen, Jurgen
AU  - Steffgen J
LA  - eng
SI  - ClinicalTrials.gov/NCT00905632
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120310
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 49717AWG6K (Ribavirin)
RN  - EC 2.7.7.48 (NS-5 protein, hepatitis C virus)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Drug Resistance, Viral
MH  - Drug Therapy, Combination
MH  - Female
MH  - Hepacivirus/*drug effects
MH  - Hepatitis C, Chronic/*drug therapy
MH  - Humans
MH  - Interferon-alpha/*administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/*administration & dosage/adverse effects/pharmacokinetics
MH  - Recombinant Proteins/administration & dosage/adverse effects/pharmacokinetics
MH  - Ribavirin/*administration & dosage/adverse effects/pharmacokinetics
MH  - Treatment Outcome
MH  - Viral Nonstructural Proteins/*antagonists & inhibitors
MH  - Young Adult
EDAT- 2012/03/15 06:00
MHDA- 2012/11/06 06:00
CRDT- 2012/03/15 06:00
PHST- 2011/08/12 00:00 [received]
PHST- 2012/02/02 00:00 [revised]
PHST- 2012/02/07 00:00 [accepted]
PHST- 2012/03/15 06:00 [entrez]
PHST- 2012/03/15 06:00 [pubmed]
PHST- 2012/11/06 06:00 [medline]
AID - S0168-8278(12)00202-4 [pii]
AID - 10.1016/j.jhep.2012.02.015 [doi]
PST - ppublish
SO  - J Hepatol. 2012 Jul;57(1):39-46. doi: 10.1016/j.jhep.2012.02.015. Epub 2012 Mar 
      10.