PMID- 27878906
OWN - NLM
STAT- MEDLINE
DCOM- 20171101
LR  - 20220331
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Linking)
VI  - 24
IP  - 4
DP  - 2017 Apr
TI  - Simeprevir, daclatasvir and sofosbuvir for hepatitis C virus-infected patients 
      with decompensated liver disease.
PG  - 287-294
LID - 10.1111/jvh.12645 [doi]
AB  - Approximately three million individuals in the United States are chronically 
      infected with hepatitis C virus (HCV). Chronic HCV infection may lead to the 
      development of compensated as well as decompensated liver cirrhosis. The Phase II 
      IMPACT study was conducted in HCV genotype 1- or 4-infected cirrhotic patients 
      with portal hypertension or decompensated liver disease and assessed for the 
      first time the combination of the three direct-acting antivirals simeprevir, 
      daclatasvir and sofosbuvir. Treatment-naive or treatment-experienced adults with 
      Child-Pugh (CP) score <7 (CP A) and evidence of portal hypertension, or CP score 
      7-9 (CP B), received 12 weeks of simeprevir 150 mg, daclatasvir 60 mg and 
      sofosbuvir 400 mg, once daily. The primary efficacy endpoint was sustained 
      virologic response 12 weeks after end of treatment (SVR12). Pharmacokinetics and 
      safety were also assessed. Overall, 40 patients were enrolled (CP A: 19; CP B: 
      21). All 40 patients achieved SVR12. At week 8, the mean pharmacokinetic exposure 
      to simeprevir, sofosbuvir, daclatasvir and GS-331007 (sofosbuvir metabolite) was 
      2.2-, 1.5-, 1.2- and 1.2-fold higher in patients with CP B than CP A, 
      respectively. Grade 1/2 adverse events (AEs) occurred in 26 of 40 (65%) patients. 
      One CP B patient had a Grade 3 AE (gastrointestinal haemorrhage), which was 
      reported as a serious AE but not considered related to study drugs. Treatment for 
      12 weeks with simeprevir, daclatasvir and sofosbuvir was generally safe and well 
      tolerated, and resulted in 100% of cirrhotic patients with portal hypertension or 
      decompensated liver disease achieving SVR12.
CI  - (c) 2017 The Authors. Journal of VIral Hepatitis published by John Wiley & Sons 
      Ltd.
FAU - Lawitz, E
AU  - Lawitz E
AD  - Texas Liver Institute, University of Texas Health Science Center, San Antonio, 
      TX, USA.
FAU - Poordad, F
AU  - Poordad F
AD  - Texas Liver Institute, University of Texas Health Science Center, San Antonio, 
      TX, USA.
FAU - Gutierrez, J A
AU  - Gutierrez JA
AD  - Texas Liver Institute, University of Texas Health Science Center, San Antonio, 
      TX, USA.
FAU - Kakuda, T N
AU  - Kakuda TN
AD  - Alios Biopharma, San Francisco, CA, USA.
FAU - Picchio, G
AU  - Picchio G
AD  - Janssen Research & Development LLC, Raritan, NJ, USA.
FAU - Beets, G
AU  - Beets G
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Vandevoorde, A
AU  - Vandevoorde A
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Van Remoortere, P
AU  - Van Remoortere P
AD  - Janssen Research & Development LLC, Titusville, NJ, USA.
FAU - Jacquemyn, B
AU  - Jacquemyn B
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Luo, D
AU  - Luo D
AD  - Janssen Research & Development LLC, Titusville, NJ, USA.
FAU - Ouwerkerk-Mahadevan, S
AU  - Ouwerkerk-Mahadevan S
AD  - Janssen Research & Development LLC, Beerse, Belgium.
FAU - Vijgen, L
AU  - Vijgen L
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Van Eygen, V
AU  - Van Eygen V
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Beumont, M
AU  - Beumont M
AD  - Janssen Research & Development LLC, Beerse, Belgium.
LA  - eng
SI  - ClinicalTrials.gov/NCT02262728
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20161123
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (Imidazoles)
RN  - 0 (Pyrrolidines)
RN  - 9WS5RD66HZ (Simeprevir)
RN  - HG18B9YRS7 (Valine)
RN  - LI2427F9CI (daclatasvir)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Carbamates
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - Hepatic Insufficiency/*etiology
MH  - Hepatitis C, Chronic/*complications/*drug therapy
MH  - Humans
MH  - Imidazoles/*administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Pyrrolidines
MH  - Simeprevir/*administration & dosage/adverse effects/pharmacokinetics
MH  - Sofosbuvir/*administration & dosage/adverse effects/pharmacokinetics
MH  - Treatment Outcome
MH  - United States
MH  - Valine/analogs & derivatives
OTO - NOTNLM
OT  - daclatasvir
OT  - hepatitis C
OT  - simeprevir
OT  - sofosbuvir
EDAT- 2016/11/24 06:00
MHDA- 2017/11/02 06:00
CRDT- 2016/11/24 06:00
PHST- 2016/08/15 00:00 [received]
PHST- 2016/10/04 00:00 [accepted]
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2017/11/02 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
AID - 10.1111/jvh.12645 [doi]
PST - ppublish
SO  - J Viral Hepat. 2017 Apr;24(4):287-294. doi: 10.1111/jvh.12645. Epub 2016 Nov 23.