PMID- 25115901
OWN - NLM
STAT- MEDLINE
DCOM- 20150928
LR  - 20220410
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Print)
IS  - 0944-1174 (Linking)
VI  - 50
IP  - 2
DP  - 2015 Feb
TI  - Vaniprevir plus peginterferon alfa-2a and ribavirin in treatment-experienced 
      Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase 
      II study.
PG  - 238-48
LID - 10.1007/s00535-014-0979-2 [doi]
AB  - BACKGROUND: Vaniprevir (MK-7009) is a hepatitis C virus (HCV) non-structural 3/4a 
      protease inhibitor which significantly increases virologic response rates in HCV 
      genotype (GT) 1-infected patients when added to peginterferon and ribavirin (PR). 
      METHODS: This was a phase II, multicenter, double-blind, randomized, dose-ranging 
      study in Japanese patients with HCV GT1 infection and previous relapse. Patients 
      received twice daily vaniprevir 100, 300, or 600 mg, or placebo plus PR for 4 
      weeks then PR alone for 2 weeks. Further treatment with PR was continued up to a 
      maximum of 72 weeks. The primary endpoint was rapid virologic response (RVR; 
      undetectable HCV RNA at treatment week 4). RESULTS: Ninety patients completed 4 
      weeks of vaniprevir/placebo plus PR. Rates of RVR were significantly higher with 
      vaniprevir compared with placebo (86, 95, and 76 % in the vaniprevir 100-, 300-, 
      and 600-mg arms versus 20 % with control; p<0.001 for all comparisons). Rates of 
      SVR, an exploratory analysis, in the vaniprevir 100-, 300-, 600-mg, and control 
      arms were 95, 100, 100, and 72 %, respectively. No patient had virologic 
      breakthrough or non-response while receiving vaniprevir. There were no serious 
      adverse events (AEs) or discontinuations due to an AE during vaniprevir 
      treatment. Diarrhea and nausea were more common with vaniprevir 600 mg than 
      control or lower vaniprevir doses. CONCLUSION: The addition of vaniprevir to PR 
      was associated with an increase in RVR and SVR. Combined with a generally safe 
      and well-tolerated profile, these data supported the further evaluation of 
      vaniprevir in Japanese patients with HCV GT1 infection (#NCT00880763).
FAU - Hayashi, Norio
AU  - Hayashi N
AD  - Kansai Rosai Hospital, 1-69 Inabasou 3-chome, Amagasaki, Hyogo, 660-8511, Japan, 
      hayashin@kanrou.net.
FAU - Mobashery, Niloufar
AU  - Mobashery N
FAU - Izumi, Namiki
AU  - Izumi N
LA  - eng
SI  - ClinicalTrials.gov/NCT00880763
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140813
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Antiviral Agents)
RN  - 0 (Cyclopropanes)
RN  - 0 (Indoles)
RN  - 0 (Interferon-alpha)
RN  - 0 (Isoindoles)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (RNA, Viral)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfonamides)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 49717AWG6K (Ribavirin)
RN  - 9DLQ4CIU6V (Proline)
RN  - CV3X74AO1H (vaniprevir)
RN  - GMW67QNF9C (Leucine)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Adult
MH  - Antiviral Agents/administration & dosage/blood/*therapeutic use
MH  - Cyclopropanes
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Resistance, Viral
MH  - Drug Therapy, Combination
MH  - Female
MH  - Genotype
MH  - Hepacivirus/drug effects/genetics/isolation & purification
MH  - Hepatitis C, Chronic/blood/*drug therapy/virology
MH  - Humans
MH  - Indoles/administration & dosage/blood/*therapeutic use
MH  - Interferon-alpha/*therapeutic use
MH  - Isoindoles
MH  - Lactams, Macrocyclic
MH  - Leucine/analogs & derivatives
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/*therapeutic use
MH  - Proline/analogs & derivatives
MH  - RNA, Viral/blood
MH  - Recombinant Proteins/therapeutic use
MH  - Ribavirin/*therapeutic use
MH  - Sulfonamides
MH  - Viral Load
MH  - Young Adult
PMC - PMC4318982
EDAT- 2014/08/15 06:00
MHDA- 2015/09/29 06:00
PMCR- 2014/08/13
CRDT- 2014/08/14 06:00
PHST- 2014/05/02 00:00 [received]
PHST- 2014/07/15 00:00 [accepted]
PHST- 2014/08/14 06:00 [entrez]
PHST- 2014/08/15 06:00 [pubmed]
PHST- 2015/09/29 06:00 [medline]
PHST- 2014/08/13 00:00 [pmc-release]
AID - 979 [pii]
AID - 10.1007/s00535-014-0979-2 [doi]
PST - ppublish
SO  - J Gastroenterol. 2015 Feb;50(2):238-48. doi: 10.1007/s00535-014-0979-2. Epub 2014 
      Aug 13.