title: Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection.
abstract: OBJECTIVE
  Therapeutic regimens are being developed for patients with hepatitis C virus (HCV) infection that do not include the combination of peginterferon alfa and ribavirin. We investigated the antiviral effect and safety of BI 201335 (an inhibitor of the NS3/4A protease) and BI 207127 (an inhibitor of the NS5B non-nucleoside polymerase) with ribavirin.
  
  
  METHODS
  Thirty-two treatment-naïve patients with chronic HCV genotype 1 infection were randomly assigned to groups that were given 400 mg or 600 mg BI 207127 3 times daily plus 120 mg BI 201335 once daily and 1000 to 1200 mg/day ribavirin for 4 weeks. The primary efficacy end point was virologic response (HCV RNA level <25 IU/mL at week 4). Thirty-two patients received treatment; 31 completed all 4 weeks of assigned combination therapy.
  
  
  RESULTS
  In the group given BI 207127 400 mg 3 times daily, the rates of virologic response were 47%, 67%, and 73% at days 15, 22, and 29; a higher rate of response was observed in patients with genotype-1b compared with genotype-1a infections. In the group given BI 207127 600 mg 3 times daily, the rates of virologic response were 82%, 100%, and 100%, respectively, and did not differ among genotypes. One patient in the group given 400 mg 3 times daily had virologic breakthrough (≥1 log(10) rebound in HCV RNA) at day 22. The most frequent adverse events were mild gastrointestinal disorders, rash, and photosensitivity. There were no severe or serious adverse events; no patients discontinued therapy prematurely.
  
  
  CONCLUSIONS
  The combination of the protease inhibitor BI 201335, the polymerase inhibitor BI 207127, and ribavirin has rapid and strong activity against HCV genotype-1 and did not cause serious or severe adverse events.
authors.affiliation: J. W. Goethe University Hospital, Frankfurt, Germany. zeuzem@em.uni-frankfurt.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Peter
authors.initials: P
authors.lastname: Angus
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Ed
authors.initials: E
authors.lastname: Gane
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
authors.forename: Ansgar
authors.initials: A
authors.lastname: Lohse
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arasteh
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Markus
authors.initials: M
authors.lastname: Heim
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
authors.forename: Gerhard
authors.initials: G
authors.lastname: Nehmiz
authors.forename: Carla
authors.initials: C
authors.lastname: Haefner
authors.forename: Wulf Otto
authors.initials: WO
authors.lastname: Boecher
mesh_terms: D000179:Acrylates / Q000009:adverse effects / Q000627:therapeutic use*; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines; D012367:RNA, Viral / Q000032:analysis / Q000097:blood / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors
chemical_list: D000179:Acrylates; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D001562:Benzimidazoles; D009842:Oligopeptides; D011480:Protease Inhibitors; D011804:Quinolines; D012367:RNA, Viral; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; D012254:Ribavirin; C000592437:deleobuvir; C552340:faldaprevir; D011392:Proline; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; D007930:Leucine