PMID- 19320234
OWN - NLM
STAT- MEDLINE
DCOM- 20090414
LR  - 20220110
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 14
IP  - 1
DP  - 2009
TI  - Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C 
      virus RNA polymerase inhibitor, after 5 days oral treatment.
PG  - 23-32
AB  - BACKGROUND: BILB 1941 is a potent and specific nonnucleoside inhibitor of the 
      hepatitis C virus (HCV) RNA polymerase in vitro. METHODS: In a double-blind 
      sequential group comparison, 96 male HCV genotype 1 patients with minimal to mild 
      liver fibrosis (Ishak or Metavir score 0-2) were randomized (8 to active 
      treatment and 2 to placebo per dose group) and treated with 10-450 mg BILB 1941 
      every 8 h over 5 days. Viral load (VL) was measured using Roche Cobas TaqMan 
      assays. RESULTS: VL decreased by > or =1 log10 IU/ml in 2/8, 2/8, 1/8, 2/7, 0/8, 
      2/8 and 4/5 patients on 60, 80, 100, 150, 200, 300 and 450 mg, respectively. No 
      response was seen with placebo. HCV subtype 1b showed better response than 1a, 
      the effect of other covariables including prior interferon treatment was not 
      significant. NS5B population sequencing and phenotyping identified baseline 
      samples with reduced BILB 1941 susceptibility, but did not detect an on-treatment 
      emergence of resistant mutants. Plasma drug levels were linear until 300 mg. No 
      serious adverse events (AEs) were reported. AEs were mainly 
      gastrointestinal-related (most frequent diarrhoea) and frequency increased with 
      dose. On 450 mg, all five active-treated patients discontinued (four for 
      gastrointestinal intolerance and one for increased aspartate aminotransferase and 
      alanine aminotransferase levels) and the trial was discontinued. CONCLUSIONS: 
      BILB 1941 monotherapy demonstrated antiviral activity against HCV genotype 1, but 
      gastrointestinal intolerance precluded testing of higher doses.
FAU - Erhardt, Andreas
AU  - Erhardt A
AD  - Klinik fur Gastroenterologie, Hepatologie and Infektiologie, Universitatsklinik 
      Dusseldorf, Dusseldorf, Germany. erhardt@uni-duesseldorf.de
FAU - Deterding, Katja
AU  - Deterding K
FAU - Benhamou, Yves
AU  - Benhamou Y
FAU - Reiser, Markus
AU  - Reiser M
FAU - Forns, Xavier
AU  - Forns X
FAU - Pol, Stanislas
AU  - Pol S
FAU - Calleja, Jose Luis
AU  - Calleja JL
FAU - Ross, Susanne
AU  - Ross S
FAU - Spangenberg, Hans Christian
AU  - Spangenberg HC
FAU - Garcia-Samaniego, Javier
AU  - Garcia-Samaniego J
FAU - Fuchs, Michael
AU  - Fuchs M
FAU - Enriquez, Jaime
AU  - Enriquez J
FAU - Wiegand, Johannes
AU  - Wiegand J
FAU - Stern, Jerry
AU  - Stern J
FAU - Wu, Kate
AU  - Wu K
FAU - Kukolj, George
AU  - Kukolj G
FAU - Marquis, Martin
AU  - Marquis M
FAU - Beaulieu, Pierre
AU  - Beaulieu P
FAU - Nehmiz, Gerhard
AU  - Nehmiz G
FAU - Steffgen, Jurgen
AU  - Steffgen J
CN  - BILB 1941 Study Group
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Viral)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 2.7.7.48 (NS-5 protein, hepatitis C virus)
RN  - EC 2.7.7.48 (RNA-Dependent RNA Polymerase)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Diarrhea/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - *Enzyme Inhibitors/administration & dosage/adverse effects/pharmacokinetics
MH  - Genotype
MH  - Headache/chemically induced
MH  - Hepacivirus/*drug effects/genetics
MH  - Hepatitis C, Chronic/*drug therapy/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - RNA, Viral/*antagonists & inhibitors/*genetics
MH  - RNA-Dependent RNA Polymerase/*antagonists & inhibitors
MH  - Sequence Analysis, RNA
MH  - Time Factors
MH  - Viral Load
MH  - Viral Nonstructural Proteins/antagonists & inhibitors/genetics
EDAT- 2009/03/27 09:00
MHDA- 2009/04/15 09:00
CRDT- 2009/03/27 09:00
PHST- 2009/03/27 09:00 [entrez]
PHST- 2009/03/27 09:00 [pubmed]
PHST- 2009/04/15 09:00 [medline]
PST - ppublish
SO  - Antivir Ther. 2009;14(1):23-32.