title: Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results.
abstract: BACKGROUND
  Faldaprevir (BI 201335) and deleobuvir (BI 207127) are direct-acting antiviral agents under development for the treatment of chronic HCV infection. This article describes the final results of the Phase Ib SOUND-C1 study that evaluated the interferon-free oral combination of faldaprevir, deleobuvir and ribavirin in 32 treatment-naive patients infected with HCV genotype 1.
  
  
  METHODS
  Patients were randomized to receive deleobuvir 400 mg (n=15) or 600 mg (n=17) three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks. Interferon-free therapy was followed by response-guided faldaprevir plus pegylated interferon-α2a/ribavirin to week 24 or 48.
  
  
  RESULTS
  At week 4, 73% (11/15) and 100% (17/17) of patients in the deleobuvir 400 mg and 600 mg groups achieved HCV RNA<25 IU/ml, respectively. During interferon-free treatment, virological breakthrough was reported in one patient and re-increase of HCV RNA in one patient. Both patients were successfully treated with interferon-containing therapy. The rate of sustained virological response 24 weeks after completion of treatment was 73% (11/15) in the deleobuvir 400 mg group and 94% (16/17) in the 600 mg group. During faldaprevir plus pegylated interferon-α2a/ribavirin treatment, the most common adverse events were pruritus (38% of patients), rash (31%) and asthenia (31%); these were severe in approximately 3% of patients.
  
  
  CONCLUSIONS
  Potent antiviral activity and favourable safety of the treatment regimen were demonstrated. Furthermore, the results suggest that patients with breakthrough at week 4 may be rescued with an interferon-containing regimen. Clinical trials.gov number NCT01132313.
authors.affiliation: JW Goethe University Hospital, Frankfurt am Main, 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 W
authors.initials: AW
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: Gerhard
authors.initials: G
authors.lastname: Nehmiz
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
authors.forename: Wulf O
authors.initials: WO
authors.lastname: Böcher
authors.forename: Federico J
authors.initials: FJ
authors.lastname: Mensa
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*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D016898:Interferon-alpha / Q000627:therapeutic use; D007930:Leucine / Q000031:analogs & derivatives; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000179:Acrylates; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D001562:Benzimidazoles; D016898:Interferon-alpha; D009842:Oligopeptides; D011804:Quinolines; D011994:Recombinant Proteins; D013844:Thiazoles; D011092:Polyethylene Glycols; D012254:Ribavirin; C000592437:deleobuvir; C552340:faldaprevir; D011392:Proline; D007930:Leucine; C100416:peginterferon alfa-2a