title: Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: Phase 3 studies.
abstract: OBJECTIVE
  Vaniprevir is a macrocyclic hepatitis C virus (HCV) non-structural (NS)3/4A protease inhibitor. The objective of these phase 3 multicenter, open-label trials was to evaluate the safety and efficacy of vaniprevir + peginterferon alfa-2b + ribavirin (PR) in Japanese patients with HCV genotype (GT)1 infection who had previously failed treatment with interferon-based regimens.
  
  
  METHODS
  Japanese patients with chronic HCV GT1 were enrolled. In PN044, patients with previous relapse or virologic breakthrough were randomized to vaniprevir (300 mg twice daily) + PR for 12 weeks followed by PR for another 12 weeks (12-week arm) or vaniprevir + PR for 24 weeks (24-week arm). In PN045, patients with previous partial/null response received vaniprevir + PR for 24 weeks. The primary endpoint was sustained virologic response at 24 weeks after completing treatment (SVR24).
  
  
  RESULTS
  In PN044 (n = 51), SVR24was 92.0% and 96.2% in the 12- and 24-week arms, respectively. In PN045 (n = 42), SVR24was 61.9% in all patients and 55.2% in previous null responders. In both studies, vaniprevir + PR was generally safe and well tolerated; the majority of adverse events were mild/moderate and included pyrexia, decreased hemoglobin, headache, nausea, pruritus, and decreased platelet count. Polymorphisms in the HCV NS3 gene at baseline (Y56, Q80, and V170) did not impact treatment outcome. Virologic failure was principally associated with the on-treatment emergence of R155 or D168 mutations.
  
  
  CONCLUSIONS
  Vaniprevir + PR is an effective, well-tolerated treatment for Japanese patients with HCV GT1 infection who failed previous interferon-based treatment. ClinicalTrials.gov Identifier NCT01405937 and NCT01405560 (Protocols PN044 and PN045).
authors.affiliation: Department of Hepatology, Toranomon Hospital, Kanagawa, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
authors.affiliation: Department of Hepatology, Toranomon Hospital, Kanagawa, Japan. fumitakas@toranomon.gr.jp.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Karino
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Fujimoto
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey, USA.|Former employee of Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Anita Y M
authors.initials: AY
authors.lastname: Howe
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Steve W
authors.initials: SW
authors.lastname: Ludmerer
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey, USA.|Former employee of Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Mobashery
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D054833:Isoindoles; D047029:Lactams, Macrocyclic; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D007211:Indoles; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D054833:Isoindoles; D047029:Lactams, Macrocyclic; D012367:RNA, Viral; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D011392:Proline; C540393:vaniprevir; C417083:peginterferon alfa-2b; D007930:Leucine
keywords: Japan; hepatitis C virus; peginterferon; ribavirin; vaniprevir