PMID- 28187751
OWN - NLM
STAT- MEDLINE
DCOM- 20170215
LR  - 20181113
IS  - 1471-230X (Electronic)
IS  - 1471-230X (Linking)
VI  - 17
IP  - 1
DP  - 2017 Feb 10
TI  - Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with 
      or without ribavirin and JNJ-56914845 in HCV genotype 1 infection.
PG  - 26
LID - 10.1186/s12876-017-0580-2 [doi]
LID - 26
AB  - BACKGROUND: A Phase 2a, open-label study (NCT01724086) was conducted to assess 
      the efficacy and safety of a once-daily, 2-direct-acting-antiviral-agent (2-DAA) 
      combination of simeprevir + TMC647055/ritonavir +/- ribavirin and of the 3-DAA 
      combination of simeprevir + TMC647055/ritonavir + JNJ-56914845 in chronic 
      hepatitis C virus genotype (GT)1-infected treatment-naive and prior-relapse 
      patients. METHODS: The study comprised four 12-week treatment panels: Panel 1 
      (n = 10; GT1a) and Panel 2-Arm 1 (n = 12; GT1b): simeprevir 75 mg once 
      daily + TMC647055 450 mg once daily/ritonavir 30 mg once daily + ribavirin 
      1000-1200 mg/day; Panel 2-Arm 2 (n = 9; GT1b): simeprevir 75 mg + TMC647055 
      450 mg/ritonavir 30 mg without ribavirin; Panel 3: simeprevir 75 mg + TMC647055 
      600 mg/ritonavir 50 mg with (Arm 1: GT1a; n = 7) or without (Arm 2: GT1b; n = 8) 
      ribavirin; Panel 4: simeprevir 75 mg + TMC647055 450 mg/ritonavir 
      30 mg + JNJ-56914845 30 mg once daily (Arm 1: n = 22; GT1a/GT1b) or 60 mg once 
      daily (Arm 2: n = 22; GT1a/GT1b). Primary endpoint was sustained virologic 
      response 12 weeks after end of treatment (12 weeks of combination treatment; 
      SVR12). RESULTS: In Panel 1 and Panel 2-Arm 1, 5/10 and 6/12 (50%) 
      GT1a/GT1b + ribavirin patients achieved SVR12, versus 3/9 (33%) GT1b without 
      ribavirin patients in Panel 2-Arm 2. In Panel 3-Arm 1 and Panel 3-Arm 2, 6/7 
      (86%) GT1a + ribavirin and 4/8 (50%) GT1b without ribavirin patients, 
      respectively, achieved SVR12. In Panel 4, 10/14 (71%) and 14/15 (93%) GT1a 
      patients in Arms 1 and 2 achieved SVR12 compared with 8/8 and 7/7 (100%) GT1b 
      patients in each arm, respectively. No deaths, serious adverse events (AEs), 
      Grade 4 AEs or AEs leading to treatment discontinuation occurred. CONCLUSIONS: 
      The 2- and 3-DAA combinations were well tolerated. High SVR rates of 93% and 100% 
      in GT1a- and GT1b-infected patients, respectively, were achieved in this study by 
      combining simeprevir with JNJ-56914845 60 mg and TMC647055/ritonavir. TRIAL 
      REGISTRATION: NCT01724086 (date of registration: September 26, 2012).
FAU - Bourgeois, Stefan
AU  - Bourgeois S
AD  - Department of Gastroenterology & Hepatology, ZNA Antwerp, Antwerpen, Belgium. 
      stefan.bourgeois@zna.be.
FAU - Van Vlierberghe, Hans
AU  - Van Vlierberghe H
AD  - Department of Hepatology and Gastroenterology, Universitair Ziekenhuis Gent, 
      Ghent, Belgium.
FAU - Moreno, Christophe
AU  - Moreno C
AD  - Liver Unit, CUB Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
FAU - Orlent, Hans
AU  - Orlent H
AD  - Department of Gastroenterology and Hepatology, AZ Sint-Jan AV Hospital, Bruges, 
      Belgium.
FAU - Nevens, Frederik
AU  - Nevens F
AD  - Department of Liver and Biliopancreatic Disorders, University Hospitals KU 
      Leuven, Leuven, Belgium.
FAU - Arasteh, Keikawus
AU  - Arasteh K
AD  - EPIMED/Vivantes-Auguste-Viktoria-Klinikum, Berlin, Germany.
FAU - Horsmans, Yves
AU  - Horsmans Y
AD  - Hepato-gastroenterology, Cliniques Universitaires Saint-Luc, Universite 
      Catholique de Louvain, Brussels, Belgium.
FAU - Schattenberg, Jorn M
AU  - Schattenberg JM
AD  - Department of Medicine, University Medical Center Mainz, Mainz, Germany.
FAU - Buggisch, Peter
AU  - Buggisch P
AD  - IFI, Liver Center Hamburg, Asklepiosklinik St. Georg, Hamburg, Germany.
FAU - Francque, Sven
AU  - Francque S
AD  - Department of Gastroenterology and Hepatology, Universitair Ziekenhuis Antwerpen, 
      Antwerp, Belgium.
FAU - Vijgen, Leen
AU  - Vijgen L
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Kakuda, Thomas N
AU  - Kakuda TN
AD  - Alios BioPharma Inc, South San Francisco, CA, USA.
FAU - Hoeben, Eva
AU  - Hoeben E
AD  - Janssen Research & Development BVBA, Beerse, Belgium.
FAU - Luo, Donghan
AU  - Luo D
AD  - Janssen Pharmaceuticals LLC, Titusville, NJ, USA.
FAU - Vandebosch, An
AU  - Vandebosch A
AD  - Janssen Research & Development BVBA, Beerse, Belgium.
FAU - Jacquemyn, Bert
AU  - Jacquemyn B
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Van Remoortere, Pieter
AU  - Van Remoortere P
AD  - Janssen Pharmaceuticals LLC, Titusville, NJ, USA.
FAU - Verloes, Rene
AU  - Verloes R
AD  - Janssen Research & Development BVBA, Beerse, Belgium.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170210
PL  - England
TA  - BMC Gastroenterol
JT  - BMC gastroenterology
JID - 100968547
RN  - 0 
      (27-cyclohexyl-12,13,16,17-tetrahydro-22-methoxy-11,17-dimethyl-10,10-dioxide-2,19-methano-3,7:4,1-dimetheno-1H,11H-14,10,2,9,11,17-benzoxathiatetraazacyclo 
      docosine-8,18(9H,15H)-dione)
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (GSK2336805)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Sulfonamides)
RN  - 49717AWG6K (Ribavirin)
RN  - 9WS5RD66HZ (Simeprevir)
RN  - HG18B9YRS7 (Valine)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/adverse effects/pharmacokinetics/*therapeutic use
MH  - Carbamates/adverse effects/pharmacokinetics/*therapeutic use
MH  - Drug Therapy, Combination
MH  - Female
MH  - Genotype
MH  - Hepatitis C, Chronic/*drug therapy/genetics
MH  - Heterocyclic Compounds, 4 or More Rings/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Ribavirin/adverse effects/pharmacokinetics/*therapeutic use
MH  - Ritonavir/adverse effects/pharmacokinetics/*therapeutic use
MH  - Simeprevir/adverse effects/pharmacokinetics/*therapeutic use
MH  - Sulfonamides/adverse effects/pharmacokinetics/*therapeutic use
MH  - Valine/adverse effects/*analogs & derivatives/pharmacokinetics/therapeutic use
PMC - PMC5303260
OTO - NOTNLM
OT  - Direct-acting antiviral agents
OT  - Efficacy
OT  - Hepatitis C virus
OT  - JNJ-56914845
OT  - Ribavirin
OT  - Safety
OT  - Simeprevir
OT  - TMC647055/ritonavir
OT  - genotype 1
EDAT- 2017/02/12 06:00
MHDA- 2017/02/16 06:00
PMCR- 2017/02/10
CRDT- 2017/02/12 06:00
PHST- 2016/10/06 00:00 [received]
PHST- 2017/01/18 00:00 [accepted]
PHST- 2017/02/12 06:00 [entrez]
PHST- 2017/02/12 06:00 [pubmed]
PHST- 2017/02/16 06:00 [medline]
PHST- 2017/02/10 00:00 [pmc-release]
AID - 10.1186/s12876-017-0580-2 [pii]
AID - 580 [pii]
AID - 10.1186/s12876-017-0580-2 [doi]
PST - epublish
SO  - BMC Gastroenterol. 2017 Feb 10;17(1):26. doi: 10.1186/s12876-017-0580-2.