PMID- 30739366
OWN - NLM
STAT- MEDLINE
DCOM- 20200722
LR  - 20200722
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 26
IP  - 6
DP  - 2019 Jun
TI  - Efficacy and safety of ruzasvir 60 mg and uprifosbuvir 450 mg for 12 weeks in 
      adults with chronic hepatitis C virus genotype 1, 2, 3, 4 or 6 infection.
PG  - 675-684
LID - 10.1111/jvh.13079 [doi]
AB  - In clinical trials, the three-drug regimen of ruzasvir (RZR) 60 mg, uprifosbuvir 
      (UPR) 450 mg and grazoprevir 100 mg, with or without ribavirin, has demonstrated 
      promising efficacy and excellent tolerability across a wide range of hepatitis C 
      virus (HCV)-infected individuals. The present study assessed the efficacy and 
      safety of the two-drug combination of RZR 60 mg plus UPR 450 mg administered for 
      12 weeks in participants with HCV genotype (GT) 1-6 infection. In this open-label 
      clinical trial, treatment-naive or -experienced and cirrhotic or noncirrhotic 
      participants with chronic HCV GT1-6 infection received RZR 60 mg plus UPR 450 mg 
      orally once daily for 12 weeks (NCT02759315/protocol PN035). The primary efficacy 
      endpoint was sustained virologic response at 12 weeks after the end of therapy 
      (SVR12). One hundred and sixty participants were enrolled. SVR12 rates were 96% 
      (52 of 54) in participants with GT1a infection; 100% (15 of 15) in those with 
      GT1b infection; 97% (28 of 29) in those with GT2 infection; 77% (30 of 39) in 
      those with GT3 infection; 90% (18 of 20) in those with GT4 infection; and 67% (2 
      of 3) in those with GT6 infection. Drug-related adverse events (AEs) reported by 
      >5% of participants were fatigue (n = 10, 6.3%) and diarrhoea (n = 9, 5.6%). Five 
      participants reported a total of 11 serious AEs, none considered drug-related. 
      One participant experienced on-treatment alanine aminotransferase/aspartate 
      aminotransferase elevations that resolved without intervention. Data from the 
      present study indicate that the combination of RZR 60 mg plus UPR 450 mg once 
      daily for 12 weeks was well tolerated overall but was effective only for certain 
      genotypes.
CI  - (c) 2019 John Wiley & Sons Ltd.
FAU - Lawitz, Eric
AU  - Lawitz E
AUID- ORCID: 0000-0002-4234-224X
AD  - University of Texas Health San Antonio, San Antonio, Texas.
FAU - Poordad, Fred
AU  - Poordad F
AD  - University of Texas Health San Antonio, San Antonio, Texas.
FAU - Anderson, Leah J
AU  - Anderson LJ
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Vesay, Michelle
AU  - Vesay M
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Kelly, Michelle M
AU  - Kelly MM
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Liu, Hong
AU  - Liu H
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Gao, Wei
AU  - Gao W
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Fernsler, Doreen
AU  - Fernsler D
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Asante-Appiah, Ernest
AU  - Asante-Appiah E
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Robertson, Michael N
AU  - Robertson MN
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Hanna, George J
AU  - Hanna GJ
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Barr, Eliav
AU  - Barr E
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Butterton, Joan
AU  - Butterton J
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Kowdley, Kris V
AU  - Kowdley KV
AD  - Swedish Medical Center, Seattle, Washington.
FAU - Hassanein, Tarek
AU  - Hassanein T
AD  - Southern California GI and Liver Center, Coronado, California.
FAU - Sahota, Amandeep
AU  - Sahota A
AD  - Kaiser Permanente Southern California, Los Angeles, California.
FAU - Gordon, Stuart C
AU  - Gordon SC
AD  - Henry Ford Hospital, Detroit, Michigan.
FAU - Yeh, Wendy W
AU  - Yeh WW
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
LA  - eng
SI  - ClinicalTrials.gov/NCT02759315
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20190312
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Antiviral Agents)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Pyrrolidines)
RN  - 0 (Thiazoles)
RN  - JW31KPS26S (uprifosbuvir)
RN  - LX752BD95Y (ruzasvir)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
MH  - Adult
MH  - Antiviral Agents/*administration & dosage/therapeutic use
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Female
MH  - Genotype
MH  - Hepacivirus/drug effects/genetics
MH  - Hepatitis C, Chronic/*drug therapy
MH  - Heterocyclic Compounds, 4 or More Rings/*administration & dosage/therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyrrolidines/*administration & dosage/therapeutic use
MH  - Sustained Virologic Response
MH  - Thiazoles/*administration & dosage/therapeutic use
MH  - Uridine/administration & dosage/*analogs & derivatives/therapeutic use
OTO - NOTNLM
OT  - NS5A protein
OT  - NS5B polymerase
OT  - genotype
OT  - hepatitis C virus
OT  - safety
EDAT- 2019/02/11 06:00
MHDA- 2020/07/23 06:00
CRDT- 2019/02/11 06:00
PHST- 2018/09/11 00:00 [received]
PHST- 2018/12/17 00:00 [revised]
PHST- 2019/01/11 00:00 [accepted]
PHST- 2019/02/11 06:00 [pubmed]
PHST- 2020/07/23 06:00 [medline]
PHST- 2019/02/11 06:00 [entrez]
AID - 10.1111/jvh.13079 [doi]
PST - ppublish
SO  - J Viral Hepat. 2019 Jun;26(6):675-684. doi: 10.1111/jvh.13079. Epub 2019 Mar 12.