title: Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1-infected patients in Japan: the DRAGON study.
abstract: BACKGROUND
  Efficacy, safety and pharmacokinetics of simeprevir (TMC435), a once-daily, noncovalent, oral hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in combination with peginterferon α-2a/ribavirin (PegIFNα-2a/RBV) for treatment-naïve, HCV genotype 1-infected patients in Japan.
  
  
  METHODS
  In a multicenter, randomized clinical trial in Japan, ninety-two patients received either simeprevir (50 or 100 mg QD) for 12 or 24 weeks with PegIFNα-2a/RBV for 24 or 48 weeks (according to response-guided therapy [RGT] criteria), or PegIFNα-2a/RBV for 48 weeks (PR48 group).
  
  
  RESULTS
  Compared with the PR48 group, plasma HCV RNA reductions in the simeprevir groups were rapid and more substantial (Week 4: -5.2, -5.2 and -2.9 log10IU/mL for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively). High rapid virologic response rates (83, 90, and 8 % for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively) led to high sustained virologic response rates (77-92 %, compared with 46 % for PR48). All but one of the simeprevir-treated patients were eligible to complete treatment after 24 weeks (RGT). Relapse rates in simeprevir-treated patients were low (8-17 %, compared with 36 % for the PR48 group). There were no notable differences in the safety profile between the simeprevir and PR48 groups.
  
  
  CONCLUSIONS
  The addition of simeprevir QD to PegIFNα-2a/RBV, as compared with PegIFNα-2a/RBV alone, demonstrated potent antiviral activity and significantly improved the rates of sustained virologic response, with a shortened 24-week treatment duration, in treatment-naive patients infected with HCV genotype 1 in Japan. Simeprevir was generally safe and well tolerated. (ClinicalTrials.gov number, NCT00996476).
authors.affiliation: Kansai Rosai Hospital, 1-69 Inabasou 3-chome, Amagasaki-shi, Hyogo, Japan, hayashin@kanrou.net.
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Chiharu
authors.initials: C
authors.lastname: Seto
authors.forename: Mai
authors.initials: M
authors.lastname: Kato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Komada
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Goto
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069616:Simeprevir; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a