title: Safety and efficacy of faldaprevir in combination with pegylated interferon α-2b and ribavirin in Japanese patients with genotype-1 chronic hepatitis C virus infection.
abstract: OBJECTIVE
  We evaluated the safety and efficacy of the hepatitis C virus (HCV) NS3/4A A protease inhibitor faldaprevir plus pegylated interferon α-2b and ribavirin (PegIFNα-2b/RBV) in Japanese patients with HCV genotype-1 infection.
  
  
  METHODS
  Treatment-naïve patients were randomized (1:1) to faldaprevir 120 mg q.d. for 12 or 24 weeks (response-guided therapy [RGT], n = 44), or faldaprevir 240 mg q.d. for 12 weeks (n = 43), each combined with PegIFNα-2b/RBV for 24 or 48 weeks (RGT). Response-guided therapy was based on early treatment success (HCV RNA <25 IU/mL at week 4 and <25 IU/mL undetected at week 8). Treatment-experienced patients received 240 mg q.d. for 24 weeks, plus PegIFNα-2b/RBV RGT (24 or 48 weeks, prior relapsers, n = 29) or PegIFNα-2b/RBV (48 weeks, 5 prior partial responders/breakthroughs, 10 prior null responders). The primary objective was safety; sustained virologic response 12 weeks post-treatment (SVR12) was a secondary end-point.
  
  
  RESULTS
  All except one patient experienced drug-related adverse events. Adverse events led to faldaprevir discontinuation in 1 (2%), 13 (20%), and 3 (6.8%) patients on faldaprevir 120 mg, faldaprevir 240 mg 12 weeks, and faldaprevir 240 mg 24 weeks, respectively. The SVR12 rates were: 86% with faldaprevir 120 mg and 74% with faldaprevir 240 mg among treatment-naïve patients; and 86%, 60%, and 40% among prior relapsers, partial responders/breakthroughs, and null responders, respectively.
  
  
  CONCLUSIONS
  In treatment-naïve Japanese patients, faldaprevir 120 mg q.d. plus PegIFNα-2b/RBV was better tolerated than faldaprevir 240 mg q.d. plus PegIFNα-2b/RBV, with at least comparable efficacy. In treatment-experienced patients, most prior relapsers achieved SVR12 with 24 weeks of faldaprevir 240 mg q.d. plus PegIFNα-2b/RBV. Clinicaltrials.gov NCT01579474.
authors.affiliation: Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.affiliation: Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Urano
authors.affiliation: Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzaki
authors.affiliation: Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Taniguchi
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield Connecticut, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Scherer
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield Connecticut, USA.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Berger
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield Connecticut, USA.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Quinson
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield Connecticut, USA.
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
authors.affiliation: Department of Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
keywords: Japanese; faldaprevir; phase III; relapser; treatment-experienced; treatment-naïve