PMID- 26353843
OWN - NLM
STAT- MEDLINE
DCOM- 20161019
LR  - 20220318
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 23
IP  - 2
DP  - 2016 Feb
TI  - Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with 
      hepatitis C virus genotype 1 infection: a randomized trial.
PG  - 80-8
LID - 10.1111/jvh.12464 [doi]
AB  - Grazoprevir (MK-5172, Merck & Co., Inc.) is a selective inhibitor of the 
      hepatitis C virus (HCV) NS3/4a protease. The aim of this study was to evaluate 
      the safety and efficacy of grazoprevir at doses of 25-100 mg/day in combination 
      with peginterferon and ribavirin (PEG-IFN/RBV). In this randomized, dose-ranging, 
      multicentre trial, treatment-naive adults with chronic HCV genotype 1 infection 
      received once-daily grazoprevir 25 mg, 50 mg or 100 mg plus PEG-IFN/RBV for 12 
      weeks. Patients with quantifiable HCV RNA (>/=25 IU/mL) at week 4 received an 
      additional 12 weeks of PEG-IFN/RBV. The primary endpoint was sustained virologic 
      response (HCV RNA <25 IU/mL 12 weeks after completing therapy [SVR12]). 
      Eighty-seven patients were randomly assigned and received >/=1 dose of therapy. 
      Median time to undetectable HCV RNA was 16 days in the 100-mg arm and 22 days in 
      the 25- and 50-mg arms. All patients except one had HCV RNA undetectable or 
      unquantifiable at week 4 and received 12 weeks of therapy. SVR12 was achieved by 
      13 of 24 (54.2%), 21 of 25 (84.0%) and 23 of 26 (88.5%) patients in the 25-, 50- 
      and 100-mg arms, respectively (per-protocol analysis). Three patients 
      discontinued as a result of nonserious adverse events (AEs) and three patients 
      experienced serious AEs. Transaminase elevations occurred in two patients (one 
      each in the 25- and 100-mg arms). CONCLUSION: These data support further study of 
      the grazoprevir 100-mg dose. Phase 3 studies of grazoprevir 100 mg in combination 
      with elbasvir are currently ongoing (NCT01710501; protocol P038).
CI  - (c) 2015 Merck. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.
FAU - Lagging, M
AU  - Lagging M
AD  - Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, 
      Gothenburg, Sweden.
FAU - Brown, A
AU  - Brown A
AD  - Imperial College Healthcare NHS Trust, St Mary's Hospital, London, UK.
FAU - Mantry, P S
AU  - Mantry PS
AD  - The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA.
FAU - Ramji, A
AU  - Ramji A
AD  - University of British Columbia, Vancouver, BC, Canada.
FAU - Weilert, F
AU  - Weilert F
AD  - Waikato District Health Board, Hamilton, New Zealand.
FAU - Vierling, J M
AU  - Vierling JM
AD  - Baylor College of Medicine, Houston, TX, USA.
FAU - Howe, A
AU  - Howe A
AD  - Merck & Co. Inc., Kenilworth, NJ, USA.
FAU - Gendrano, I N 3rd
AU  - Gendrano IN 3rd
AD  - Merck & Co. Inc., Kenilworth, NJ, USA.
FAU - Hwang, P
AU  - Hwang P
AD  - Merck & Co. Inc., Kenilworth, NJ, USA.
FAU - Zhang, B
AU  - Zhang B
AD  - Merck & Co. Inc., Kenilworth, NJ, USA.
FAU - Wahl, J
AU  - Wahl J
AD  - Merck & Co. Inc., Kenilworth, NJ, USA.
FAU - Robertson, M
AU  - Robertson M
AD  - Merck & Co. Inc., Kenilworth, NJ, USA.
FAU - Mobashery, N
AU  - Mobashery N
AD  - Merck & Co. Inc., Kenilworth, NJ, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01710501
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150910
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Amides)
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (Cyclopropanes)
RN  - 0 (Interferon-alpha)
RN  - 0 (NS3 protein, hepatitis C virus)
RN  - 0 (NS4A protein, flavivirus)
RN  - 0 (Quinoxalines)
RN  - 0 (RNA, Viral)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfonamides)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 49717AWG6K (Ribavirin)
RN  - 4O2AB118LA (grazoprevir)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amides
MH  - Antiviral Agents/*therapeutic use
MH  - Carbamates
MH  - Cyclopropanes
MH  - Drug Therapy, Combination/adverse effects
MH  - Female
MH  - Genotype
MH  - Hepacivirus/*drug effects/genetics
MH  - Hepatitis C, Chronic/*drug therapy
MH  - Humans
MH  - Interferon-alpha/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/adverse effects/*therapeutic use
MH  - Quinoxalines/adverse effects/*therapeutic use
MH  - RNA, Viral
MH  - Recombinant Proteins/adverse effects/therapeutic use
MH  - Ribavirin/adverse effects/*therapeutic use
MH  - Sulfonamides
MH  - Viral Load
MH  - Viral Nonstructural Proteins/antagonists & inhibitors
MH  - Young Adult
OTO - NOTNLM
OT  - adverse event
OT  - clinical trial
OT  - direct-acting antiviral drugs
OT  - resistance
OT  - sustained virologic response
EDAT- 2015/09/12 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/09/11 06:00
PHST- 2015/06/29 00:00 [received]
PHST- 2015/08/12 00:00 [accepted]
PHST- 2015/09/11 06:00 [entrez]
PHST- 2015/09/12 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - 10.1111/jvh.12464 [doi]
PST - ppublish
SO  - J Viral Hepat. 2016 Feb;23(2):80-8. doi: 10.1111/jvh.12464. Epub 2015 Sep 10.