PMID- 27291249
OWN - NLM
STAT- MEDLINE
DCOM- 20171103
LR  - 20220318
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 23
IP  - 10
DP  - 2016 Oct
TI  - Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in 
      treatment-naive patients with hepatitis C virus genotype 1 infection.
PG  - 789-97
LID - 10.1111/jvh.12552 [doi]
AB  - Grazoprevir (GZR) is a second-generation hepatitis C virus NS3/4A protease 
      inhibitor. The aim of this study was to evaluate GZR plus ribavirin (RBV) in 
      patients with HCV GT1 infection. Noncirrhotic, IL28B CC patients with HCV 
      genotype 1 infection were randomized to GZR 100 mg once daily and RBV for 12 or 
      24 weeks. Patients in the 12-week arm with detectable HCV RNA at treatment week 4 
      (TW4) had treatment extended to 24 weeks (response-guided therapy, RGT). The 
      primary endpoint was sustained virologic response (SVR12) at follow-up week 12 
      (HCV RNA <25 IU/mL) in the per-protocol (PP) population (excluding patients with 
      important protocol deviations). Twenty-six patients were randomized and 22 were 
      included in the PP population. SVR12 was 58.3% (7 of 12) and 90% (9 of 10) in the 
      RGT and 24-week arms, respectively. Seven PP patients had virologic failure, 
      including one patient in the 24-week arm who relapsed after follow-up week 12. 
      All three breakthrough patients had wild-type (WT) virus at baseline and 
      developed breakthrough at TW6 or TW12 with Y56H, A156T and D168A/N mutations. Of 
      the five relapse patients, four had WT at baseline (at relapse three had WT and 
      one had V55A and D168A), and one had S122A/T at baseline and S122T at relapse. 
      There were no serious adverse events (AEs), discontinuations due to AEs or grade 
      3/4 elevations in total and/or direct bilirubin. Grazoprevir plus RBV was 
      associated with a rapid and sustained suppression of HCV RNA. These results 
      support further evaluation of grazoprevir-based regimens (NCT01716156; protocol 
      P039).
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Gane, E
AU  - Gane E
AD  - Auckland Clinical Studies, Auckland, New Zealand. edgane@adhb.govt.nz.
FAU - Ben Ari, Z
AU  - Ben Ari Z
AD  - Liver Disease Center, Sheba Medical Center, Ramat Gan, Israel.
AD  - The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Mollison, L
AU  - Mollison L
AD  - Fremantle Hepatitis Services, Fremantle Hospital, Fremantle, WA, Australia.
FAU - Zuckerman, E
AU  - Zuckerman E
AD  - Liver Unit, Carmel Medical Center Technion Faculty of Medicine, Haifa, Israel.
FAU - Bruck, R
AU  - Bruck R
AD  - Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical 
      Center, Tel Aviv, Israel.
FAU - Baruch, Y
AU  - Baruch Y
AD  - Liver Unit, Rambam Healthcare Campus and the Technion Faculty of Medicine, Haifa, 
      Israel.
FAU - Howe, A Y M
AU  - Howe AY
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Wahl, J
AU  - Wahl J
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Bhanja, S
AU  - Bhanja S
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Hwang, P
AU  - Hwang P
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Zhao, Y
AU  - Zhao Y
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
FAU - Robertson, M N
AU  - Robertson MN
AD  - Merck & Co., Inc., Kenilworth, NJ, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01716156
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160612
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 (Quinoxalines)
RN  - 0 (Sulfonamides)
RN  - 49717AWG6K (Ribavirin)
RN  - 4O2AB118LA (grazoprevir)
SB  - IM
MH  - Adult
MH  - Amides
MH  - Antiviral Agents/adverse effects/*therapeutic use
MH  - Carbamates
MH  - Cyclopropanes
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology
MH  - Female
MH  - *Genotype
MH  - Hepacivirus/*classification/*genetics/isolation & purification
MH  - Hepatitis C, Chronic/*drug therapy/virology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Quinoxalines/adverse effects/*therapeutic use
MH  - Recurrence
MH  - Ribavirin/adverse effects/*therapeutic use
MH  - Sulfonamides
MH  - Sustained Virologic Response
MH  - Treatment Outcome
OTO - NOTNLM
OT  - adverse event
OT  - clinical trial
OT  - efficacy
OT  - randomized
OT  - resistance
EDAT- 2016/06/14 06:00
MHDA- 2017/11/04 06:00
CRDT- 2016/06/14 06:00
PHST- 2016/02/29 00:00 [received]
PHST- 2016/04/10 00:00 [accepted]
PHST- 2016/06/14 06:00 [entrez]
PHST- 2016/06/14 06:00 [pubmed]
PHST- 2017/11/04 06:00 [medline]
AID - 10.1111/jvh.12552 [doi]
PST - ppublish
SO  - J Viral Hepat. 2016 Oct;23(10):789-97. doi: 10.1111/jvh.12552. Epub 2016 Jun 12.