PMID- 24316262 OWN - NLM STAT- MEDLINE DCOM- 20140527 LR - 20181202 IS - 1528-0012 (Electronic) IS - 0016-5085 (Linking) VI - 146 IP - 3 DP - 2014 Mar TI - Telaprevir twice daily is noninferior to telaprevir every 8 hours for patients with chronic hepatitis C. PG - 744-753.e3 LID - S0016-5085(13)01728-9 [pii] LID - 10.1053/j.gastro.2013.11.047 [doi] AB - BACKGROUND & AIMS: 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. CI - Copyright (c) 2014 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Buti, Maria AU - Buti M AD - Liver Unit, Department of Internal Medicine, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain. Electronic address: mbuti@vhebron.net. FAU - Agarwal, Kosh AU - Agarwal K AD - Institute of Liver Studies, Kings College Hospital, London, England. FAU - Horsmans, Yves AU - Horsmans Y AD - Clinical Pharmacology Unit, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium. FAU - Sievert, William AU - Sievert W AD - Gastroenterology and Hepatology Unit, Monash Medical Centre and Monash University, Melbourne, Australia. FAU - Janczewska, Ewa AU - Janczewska E AD - Outpatients Clinic for Hepatology, Outpatients Clinic for Hepatology, ID Clinic, Myslowice, Poland. FAU - Zeuzem, Stefan AU - Zeuzem S AD - Department of Medicine I, Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany. FAU - Nyberg, Lisa AU - Nyberg L AD - Hepatology Research Department, Kaiser Permanente, San Diego, California. FAU - Brown, Robert S Jr AU - Brown RS Jr AD - Department of Hepatology and Gastroenterology, Columbia University College of Physicians and Surgeons, New York, New York. FAU - Hezode, Christophe AU - Hezode C AD - Department of Hepatology and Gastroenterology, Hopital Henri Mondor, Creteil, France. FAU - Rizzetto, Mario AU - Rizzetto M AD - Department of Hepatology and Gastroenterology, University of Torino, Torino, Italy. FAU - Parana, Raymundo AU - Parana R AD - Gastro-Hepatology Unit, Medical School, Federal University of Bahia, Bahia, Brazil. FAU - De Meyer, Sandra AU - De Meyer S AD - Janssen Infectious Diseases BVBA, Beerse, Belgium. FAU - De Masi, Ralph AU - De Masi R AD - Janssen Research & Development LLC, Titusville, New Jersey. FAU - Luo, Donghan AU - Luo D AD - Janssen Research & Development LLC, Titusville, New Jersey. FAU - Bertelsen, Kirk AU - Bertelsen K AD - Janssen Research & Development LLC, Titusville, New Jersey. FAU - Witek, James AU - Witek J AD - Janssen Research & Development LLC, Titusville, New Jersey. LA - eng SI - ClinicalTrials.gov/NCT01241760 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20131204 PL - United States TA - Gastroenterology JT - Gastroenterology JID - 0374630 RN - 0 (Antiviral Agents) RN - 0 (Interferon-alpha) RN - 0 (Oligopeptides) RN - 0 (RNA, Viral) RN - 0 (Recombinant Proteins) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 49717AWG6K (Ribavirin) RN - 655M5O3W0U (telaprevir) RN - Q46947FE7K (peginterferon alfa-2a) SB - IM MH - Adult MH - Antiviral Agents/*administration & dosage/adverse effects/*therapeutic use MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Fatigue/epidemiology MH - Female MH - Genotype MH - Headache/epidemiology MH - Hepacivirus/genetics MH - Hepatitis C, Chronic/blood/*drug therapy MH - Humans MH - Incidence MH - Interferon-alpha/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Nausea/epidemiology MH - Oligopeptides/*administration & dosage/adverse effects/*therapeutic use MH - Polyethylene Glycols/adverse effects/*therapeutic use MH - RNA, Viral/blood MH - Recombinant Proteins/adverse effects/therapeutic use MH - Ribavirin/adverse effects/*therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - Clinical Trial OT - DAA OT - OPTIMIZE OT - Protease Inhibitor EDAT- 2013/12/10 06:00 MHDA- 2014/05/28 06:00 CRDT- 2013/12/10 06:00 PHST- 2013/07/08 00:00 [received] PHST- 2013/11/15 00:00 [revised] PHST- 2013/11/24 00:00 [accepted] PHST- 2013/12/10 06:00 [entrez] PHST- 2013/12/10 06:00 [pubmed] PHST- 2014/05/28 06:00 [medline] AID - S0016-5085(13)01728-9 [pii] AID - 10.1053/j.gastro.2013.11.047 [doi] PST - ppublish SO - Gastroenterology. 2014 Mar;146(3):744-753.e3. doi: 10.1053/j.gastro.2013.11.047. Epub 2013 Dec 4.