title: Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study.
abstract: BACKGROUND
  Vaniprevir is a potent macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. This phase III study evaluated the safety and efficacy of vaniprevir in combination with peginterferon alfa-2b and ribavirin (PR) for 24 weeks compared with PR alone for 48 weeks in treatment-naive Japanese patients with HCV genotype 1 infection.
  
  
  METHODS
  Treatment-naive Japanese patients with HCV genotype 1 infection were randomly assigned to receive vaniprevir (300 mg twice daily) plus PR for 12 weeks then PR alone for 12 weeks, vaniprevir (300 mg twice daily) plus PR for 24 weeks, or PR alone for 48 weeks. The primary end point was sustained virologic response 24 weeks after completion of treatment (SVR24).
  
  
  RESULTS
  In total, 294 patients were randomly assigned to receive treatment. Most patients had HCV genotype 1b infection (98 %, 288 of 294 patients). SVR24 was achieved in 83.7, 84.5, and 55.1 % of the patients in the vaniprevir 12-week, vaniprevir 24-week, and control arms, respectively. The difference in SVR24 rates between each vaniprevir arm and the control arm was statistically significant (p < 0.001 for both). Relapse was commoner in the control arm (29.5 %) than in the vaniprevir arms (8.6 % and 10.5 % for the 12-week and 24-week arms, respectively). Commonly reported adverse events were generally similar across treatment arms, with the exception of an increase in the incidence of gastrointestinal adverse events such as nausea, diarrhea, and vomiting in patients receiving vaniprevir. These events were considered manageable.
  
  
  CONCLUSIONS
  Vaniprevir is a valuable addition to the therapeutic options available to Japanese patients with HCV genotype 1 infection who are eligible for interferon-based treatment. CLINICALTRIALS.
  NCT01370642.
authors.affiliation: Kansai Rosai Hospital, 1-69 Inabasou 3-chome, Amagasaki, Hyogo, 660-8511, Japan. hayashin@kanrou.net.
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-Ku, Fukuoka, 810-8563, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Department of Hepatology, Toranomon Hospital, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki, 213-8587, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: MSD K.K., 1-13-12 Kudan-kita, Chiyoda-Ku, Tokyo, 102-8667, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takase
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Anita Yee Mei
authors.initials: AY
authors.lastname: Howe
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Ludmerer
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Mobashery
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D054833:Isoindoles; D007564:Japan; D047029:Lactams, Macrocyclic; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011392:Proline / Q000031:analogs & derivatives; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage; D013449:Sulfonamides; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D007211:Indoles; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D054833:Isoindoles; D047029:Lactams, Macrocyclic; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D011392:Proline; C540393:vaniprevir; C417083:peginterferon alfa-2b; D007930:Leucine
keywords: Hepatitis C virus; Japan; Peginterferon; Ribavirin; Vaniprevir