title: Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients.
abstract: Approximately 2 million Japanese individuals are infected with hepatitis C virus and are at risk for cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Patients in whom interferon (IFN)/ribavirin (RBV) therapy has failed remain at risk as effective therapeutic options are limited. This phase 2, randomized, open-label study evaluated an IFN- and RBV-free regimen of once-daily ombitasvir (ABT-267), an NS5A inhibitor, plus paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (paritaprevir/ritonavir), in pegylated IFN/RBV treatment-experienced Japanese patients with hepatitis C virus subtype 1b or genotype 2 infection. Patients without cirrhosis (aged 18-75 years) with subtype 1b infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 or 24 weeks; patients with genotype 2 infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 weeks. Sustained virologic response (SVR) at posttreatment week 24 (SVR24 ) was the primary endpoint. Adverse events were collected throughout the study. One hundred ten patients received ≥1 dose of study medication. In the subtype 1b cohort, SVR24 rates were high (88.9%-100%) regardless of paritaprevir dose or treatment duration. In the genotype 2 cohort, SVR24 rates were 57.9% and 72.2% with 100 mg and 150 mg of paritaprevir, respectively. The SVR24 rate was higher in patients with subtype 2a (90%) than 2b (27%). Concordance between SVR12 and SVR24 was 100%. The most common adverse events overall were nasopharyngitis (29%) and headache (14%).
  
  
  CONCLUSIONS
  In this difficult-to-treat population of patients in whom prior pegylated IFN/RBV had failed, ombitasvir/paritaprevir/ritonavir demonstrated potent antiviral activity with a favorable safety profile among Japanese patients with hepatitis C virus genotype 1b or 2a infection.
authors: Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan.
authors: Kazuaki
authors: K
authors: Chayama
authors: Kazuo
authors: K
authors: Notsumata
authors: Masayuki
authors: M
authors: Kurosaki
authors: Ken
authors: K
authors: Sato
authors: Lino
authors: L
authors: Rodrigues
authors: Carolyn
authors: C
authors: Setze
authors: Prajakta
authors: P
authors: Badri
authors: Tami
authors: T
authors: Pilot-Matias
authors: Regis A
authors: RA
authors: Vilchez
authors: Hiromitsu
authors: H
authors: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000813:Anilides / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates / Q000008:administration & dosage*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons; D047029:Lactams, Macrocyclic; D008103:Liver Cirrhosis; D047028:Macrocyclic Compounds / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D012254:Ribavirin; D019438:Ritonavir / Q000008:administration & dosage*; D013449:Sulfonamides; D014633:Valine; D055815:Young Adult
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D007372:Interferons; D011392:Proline; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir
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