title: Telaprevir twice daily is noninferior to telaprevir every 8 hours for patients with chronic hepatitis C.
abstract: OBJECTIVE
  We performed an open-label, multicenter, phase 3 study of the safety and efficacy of twice-daily telaprevir in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with cirrhosis.
  
  
  METHODS
  Patients were randomly assigned to groups treated with telaprevir 1125 mg twice daily or 750 mg every 8 hours plus peginterferon alfa-2a and ribavirin for 12 weeks; patients were then treated with peginterferon alfa-2a and ribavirin alone for 12 weeks if their level of HCV RNA at week 4 was <25 IU/mL or for 36 weeks if their level was higher. The primary objective was to demonstrate noninferiority of telaprevir twice daily versus every 8 hours in producing a sustained virological response 12 weeks after the end of therapy (SVR12) (based on a -11% lower limit of the 95% lower confidence interval for the difference between groups).
  
  
  RESULTS
  At baseline, of 740 patients, 85% had levels of HCV RNA ≥800,000 IU/mL, 28% had fibrosis (F3-F4), 14% had cirrhosis (F4), 57% were infected with HCV genotype 1a, and 71% had the non-CC IL28B genotype. Of patients who were treated with telaprevir twice daily, 74.3% achieved SVR12 compared with 72.8% of patients who were treated with telaprevir every 8 hours (difference in response, 1.5%; 95% confidence interval, -4.9% to 12.0%), so telaprevir twice daily is noninferior to telaprevir every 8 hours. All subgroups of patients who were treated with telaprevir twice daily versus those who were treated every 8 hours had similar rates of SVR12. The most frequent adverse events (AEs) in the telaprevir phase were fatigue (47%), pruritus (43%), anemia (42%), nausea (37%), rash (35%), and headache (26%); serious AEs were reported in 9% of patients. Rates of AEs and serious AEs were similar or slightly higher among patients treated with telaprevir every 8 hours.
  
  
  CONCLUSIONS
  Based on a phase 3 trial, telaprevir twice daily is noninferior to every 8 hours in producing SVR12, with similar levels of safety and tolerability. These results support use of telaprevir twice daily in patients with chronic HCV genotype 1 infection, including those with cirrhosis. ClinicalTrials.gov, Number: NCT01241760.
authors: Liver Unit, Department of Internal Medicine, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain. Electronic address: mbuti@vhebron.net.
authors: Maria
authors: M
authors: Buti
authors: Institute of Liver Studies, Kings College Hospital, London, England.
authors: Kosh
authors: K
authors: Agarwal
authors: Clinical Pharmacology Unit, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors: Yves
authors: Y
authors: Horsmans
authors: Gastroenterology and Hepatology Unit, Monash Medical Centre and Monash University, Melbourne, Australia.
authors: William
authors: W
authors: Sievert
authors: Outpatients Clinic for Hepatology, Outpatients Clinic for Hepatology, ID Clinic, Myslowice, Poland.
authors: Ewa
authors: E
authors: Janczewska
authors: Department of Medicine I, Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany.
authors: Stefan
authors: S
authors: Zeuzem
authors: Hepatology Research Department, Kaiser Permanente, San Diego, California.
authors: Lisa
authors: L
authors: Nyberg
authors: Department of Hepatology and Gastroenterology, Columbia University College of Physicians and Surgeons, New York, New York.
authors: Robert S
authors: RS
authors: Brown
authors: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Créteil, France.
authors: Christophe
authors: C
authors: Hézode
authors: Department of Hepatology and Gastroenterology, University of Torino, Torino, Italy.
authors: Mario
authors: M
authors: Rizzetto
authors: Gastro-Hepatology Unit, Medical School, Federal University of Bahia, Bahia, Brazil.
authors: Raymundo
authors: R
authors: Paraná
authors: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors: Sandra
authors: S
authors: De Meyer
authors: Janssen Research & Development LLC, Titusville, New Jersey.
authors: Ralph
authors: R
authors: De Masi
authors: Janssen Research & Development LLC, Titusville, New Jersey.
authors: Donghan
authors: D
authors: Luo
authors: Janssen Research & Development LLC, Titusville, New Jersey.
authors: Kirk
authors: K
authors: Bertelsen
authors: Janssen Research & Development LLC, Titusville, New Jersey.
authors: James
authors: J
authors: Witek
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006261:Headache / Q000453:epidemiology; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000453:epidemiology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a
keywords: Clinical Trial; DAA; OPTIMIZE; Protease Inhibitor