PMID- 26957110
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20211204
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 23
IP  - 8
DP  - 2016 Aug
TI  - GS-9857 in patients with chronic hepatitis C virus genotype 1-4 infection: a 
      randomized, double-blind, dose-ranging phase 1 study.
PG  - 614-22
LID - 10.1111/jvh.12527 [doi]
AB  - GS-9857, an inhibitor of the hepatitis C virus (HCV) nonstructural protein (NS) 
      3/4A, demonstrates potent activity against HCV genotypes 1-6 and improved 
      coverage against commonly encountered NS3 resistance-associated variants (RAVs). 
      In this study, the safety, tolerability, antiviral activity and pharmacokinetics 
      (PK) of GS-9857 were evaluated in patients with chronic HCV genotype 1-4 
      infection. Patients with genotype 1-4 infection received placebo or once-daily 
      GS-9857 at doses ranging from 50 to 300 mg for 3 days under fasting conditions. 
      GS-9857 was well tolerated; all reported adverse events (AEs) were mild or 
      moderate in severity. Diarrhoea and headache were the most commonly reported AEs. 
      Grade 3 or 4 laboratory abnormalities were observed in 17% of patients receiving 
      GS-9857; there were no Grade 3 or 4 abnormalities in alanine aminotransferase, 
      aspartate aminotransferase or alkaline phosphatase levels. GS-9857 demonstrated 
      potent antiviral activity in patients with chronic HCV infection, achieving mean 
      and median maximum reductions in HCV RNA of >/=3 log10 IU/mL following 
      administration of a 100-mg dose in patients with HCV genotype 1a, 1b, 2, 3 or 4 
      infection. The antiviral activity of GS-9857 was unaffected by the presence of 
      pretreatment NS3 RAVs. In patients with genotype 1-4 infection, GS-9857 exhibited 
      linear PK and was associated with a median half-life of 29-42 h, supporting 
      once-daily dosing. Thus, the tolerability, efficacy and pharmacokinetic profile 
      of GS-9857 support its further evaluation for treatment of patients with chronic 
      HCV infection.
CI  - (c) 2016 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons 
      Ltd.
FAU - Rodriguez-Torres, M
AU  - Rodriguez-Torres M
AD  - Fundacion de Investigacion, Rio Piedras, Puerto Rico.
FAU - Glass, S
AU  - Glass S
AD  - PRA Health Sciences, Philadelphia, PA, USA.
FAU - Hill, J
AU  - Hill J
AD  - Avail Clinical Research, LLC, DeLand, FL, USA.
FAU - Freilich, B
AU  - Freilich B
AD  - Kansas City Research Institute, Kansas City, MO, USA.
FAU - Hassman, D
AU  - Hassman D
AD  - Comprehensive Clinical Research, Berlin, NJ, USA.
FAU - Di Bisceglie, A M
AU  - Di Bisceglie AM
AD  - Saint Louis University Medical Center, Saint Louis, MO, USA.
FAU - Taylor, J G
AU  - Taylor JG
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Kirby, B J
AU  - Kirby BJ
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Dvory-Sobol, H
AU  - Dvory-Sobol H
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Yang, J C
AU  - Yang JC
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - An, D
AU  - An D
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Stamm, L M
AU  - Stamm LM
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Brainard, D M
AU  - Brainard DM
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Kim, S
AU  - Kim S
AD  - WCCT Global, Costa Mesa, CA, USA.
FAU - Krefetz, D
AU  - Krefetz D
AD  - PRA Health Sciences, Marlton, NJ, USA.
FAU - Smith, W
AU  - Smith W
AD  - New Orleans Center for Clinical Research, University of Tennessee Medical Center, 
      Knoxville, TN, USA.
FAU - Marbury, T
AU  - Marbury T
AD  - Orlando Clinical Research Center, Orlando, FL, USA.
FAU - Lawitz, E
AU  - Lawitz E
AD  - Texas Liver Institute, University of Texas Health Science Center, San Antonio, 
      TX, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160309
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Aminoisobutyric Acids)
RN  - 0 (Antiviral Agents)
RN  - 0 (Cyclopropanes)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Macrocyclic Compounds)
RN  - 0 (Placebos)
RN  - 0 (Quinoxalines)
RN  - 0 (Sulfonamides)
RN  - 0570F37359 (voxilaprevir)
RN  - 9DLQ4CIU6V (Proline)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aminoisobutyric Acids
MH  - Antiviral Agents/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Cyclopropanes
MH  - Double-Blind Method
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - *Genotype
MH  - Hepacivirus/*classification/*genetics/isolation & purification
MH  - Hepatitis C, Chronic/*drug therapy/*virology
MH  - Humans
MH  - Lactams, Macrocyclic
MH  - Leucine/analogs & derivatives
MH  - Macrocyclic Compounds/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Placebos/administration & dosage
MH  - Proline/analogs & derivatives
MH  - Quinoxalines
MH  - Sulfonamides/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Treatment Outcome
MH  - Viral Load
MH  - Young Adult
OTO - NOTNLM
OT  - GS-9857
OT  - NS3/4A protease inhibitor
OT  - hepatitis C virus
EDAT- 2016/03/10 06:00
MHDA- 2017/10/31 06:00
CRDT- 2016/03/10 06:00
PHST- 2016/01/22 00:00 [received]
PHST- 2016/02/18 00:00 [accepted]
PHST- 2016/03/10 06:00 [entrez]
PHST- 2016/03/10 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
AID - 10.1111/jvh.12527 [doi]
PST - ppublish
SO  - J Viral Hepat. 2016 Aug;23(8):614-22. doi: 10.1111/jvh.12527. Epub 2016 Mar 9.