PMID- 23856779
OWN - NLM
STAT- MEDLINE
DCOM- 20140409
LR  - 20211021
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 57
IP  - 10
DP  - 2013 Oct
TI  - Antiviral effect, safety, and pharmacokinetics of five-day oral administration of 
      Deleobuvir (BI 207127), an investigational hepatitis C virus RNA polymerase 
      inhibitor, in patients with chronic hepatitis C.
PG  - 4727-35
LID - 10.1128/AAC.00565-13 [doi]
AB  - Deleobuvir (BI 207127) is an investigational oral nonnucleoside inhibitor of 
      hepatitis C virus (HCV) NS5B RNA polymerase. Antiviral activity, virology, 
      pharmacokinetics, and safety were assessed in HCV genotype 1-infected patients 
      receiving 5 days' deleobuvir monotherapy. In this double-blind phase 1b study, 
      treatment-naive (TN; n = 15) and treatment-experienced (TE; n = 45) patients 
      without cirrhosis received placebo or deleobuvir at 100, 200, 400, 800, or 1,200 
      mg every 8 h (q8h) for 5 days. Patients with cirrhosis (n = 13) received 
      deleobuvir at 400 or 600 mg q8h for 5 days. Virologic analyses included NS5B 
      genotyping and phenotyping of individual isolates. At day 5, patients without 
      cirrhosis had dose-dependent median HCV RNA reductions of up to 3.8 log10 (with 
      no placebo response); patients with cirrhosis had median HCV RNA reductions of 
      approximately 3.0 log10. Three patients discontinued due to adverse events (AEs). 
      The most common AEs were gastrointestinal, nervous system, and skin/cutaneous 
      tissue disorders. Plasma exposure of deleobuvir was supraproportional at doses >/= 
      400 mg q8h and approximately 2-fold higher in patients with cirrhosis than in 
      patients without cirrhosis. No virologic breakthrough was observed. NS5B 
      substitutions associated with deleobuvir resistance in vitro were detected in 
      9/59 patients; seven encoded P495 substitutions, including P495L, which conferred 
      120- to 310-fold-decreased sensitivity to deleobuvir. P495 variants did not 
      persist in follow-up without selective drug pressure. Deleobuvir monotherapy was 
      generally well tolerated and demonstrated dose-dependent antiviral activity 
      against HCV genotype 1 over 5 days.
FAU - Larrey, Dominique
AU  - Larrey D
AD  - Departement d'Hepato-Gastroenterologie, Hopital Saint Eloi, Montpellier, France.
FAU - Lohse, Ansgar W
AU  - Lohse AW
FAU - Trepo, Christian
AU  - Trepo C
FAU - Bronowicki, Jean-Pierre
AU  - Bronowicki JP
FAU - Arasteh, Keikawus
AU  - Arasteh K
FAU - Bourliere, Marc
AU  - Bourliere M
FAU - Calleja, Jose Luis
AU  - Calleja JL
FAU - Stern, Jerry O
AU  - Stern JO
FAU - Nehmiz, Gerhard
AU  - Nehmiz G
FAU - Abdallah, Nasri
AU  - Abdallah N
FAU - Berger, Kristi L
AU  - Berger KL
FAU - Marquis, Martin
AU  - Marquis M
FAU - Steffgen, Jurgen
AU  - Steffgen J
FAU - Kukolj, George
AU  - Kukolj G
CN  - BI 207127 Study Group
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20130715
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antiviral Agents)
RN  - EC 2.7.7.6 (DNA-Directed RNA Polymerases)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/adverse effects/*pharmacokinetics/*therapeutic use
MH  - DNA-Directed RNA Polymerases/antagonists & inhibitors
MH  - Double-Blind Method
MH  - Female
MH  - Hepacivirus/*drug effects/*enzymology/genetics
MH  - Hepatitis C, Chronic/*drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Young Adult
PMC - PMC3811456
EDAT- 2013/07/17 06:00
MHDA- 2014/04/10 06:00
PMCR- 2014/04/01
CRDT- 2013/07/17 06:00
PHST- 2013/07/17 06:00 [entrez]
PHST- 2013/07/17 06:00 [pubmed]
PHST- 2014/04/10 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - AAC.00565-13 [pii]
AID - 00565-13 [pii]
AID - 10.1128/AAC.00565-13 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2013 Oct;57(10):4727-35. doi: 10.1128/AAC.00565-13. 
      Epub 2013 Jul 15.