A total of 259 patients were enrolled at 24 centers in Japan from January 5 2012 to March 30 2012. Eligible patients were men and women, 20 to 75 years of age, with chronic HCV genotype 1b infection, an HCV RNA level of 105 IU/mL or higher, with a body-mass index of 16 to 35 kg/m2, and, in up to 10% of enrolled patients, evidence of compensated cirrhosis (Child-Pugh A), as documented either by liver biopsy or discriminated by a previously described algorithm.14 (link)
Key exclusion criteria included evidence of hepatocellular carcinoma, coinfection with hepatitis B virus or human immunodeficiency virus, or previous exposure to inhibitors of NS5A or NS3 protease. Patients with alanine aminotransferase (ALT) of more than 5 times the upper limit of normal range, total bilirubin of 2 mg/dL or higher, an international normalized ratio of 1.7 or higher, an albumin level 3.5 g/dL or below, and a platelet count of less than 50,000/mm3 were also excluded.
Patients ineligible for interferon-based therapy, but potentially eligible for enrolment in this study, were treatment-naïve and considered poor candidates for interferon-based therapy because of medical complications including anemia, neutropenia, thrombocytopenia, depression, advanced age (≥65 years), or other conditions deemed not suitable for interferon-based therapy by the investigator, including hypertension, diabetes mellitus, autoimmune disease, and abnormal thyroid function. Patients intolerant to interferon-based therapy had received interferon-based therapy for less than 12 weeks and previously discontinued from therapy due to toxicities associated with interferon or ribavirin. Patients who were null or partial responders to previous peginterferon/ribavirin or interferon-beta/ribavirin therapy were defined as never having attained an undetectable HCV RNA level after at least 12 weeks of therapy. Null responders included patients who never attained at least a 2-log10 decrease from baseline in HCV RNA levels at week 12, and partial responders never achieved undetectable HCV RNA levels after 12 weeks of therapy.
Key exclusion criteria included evidence of hepatocellular carcinoma, coinfection with hepatitis B virus or human immunodeficiency virus, or previous exposure to inhibitors of NS5A or NS3 protease. Patients with alanine aminotransferase (ALT) of more than 5 times the upper limit of normal range, total bilirubin of 2 mg/dL or higher, an international normalized ratio of 1.7 or higher, an albumin level 3.5 g/dL or below, and a platelet count of less than 50,000/mm3 were also excluded.
Patients ineligible for interferon-based therapy, but potentially eligible for enrolment in this study, were treatment-naïve and considered poor candidates for interferon-based therapy because of medical complications including anemia, neutropenia, thrombocytopenia, depression, advanced age (≥65 years), or other conditions deemed not suitable for interferon-based therapy by the investigator, including hypertension, diabetes mellitus, autoimmune disease, and abnormal thyroid function. Patients intolerant to interferon-based therapy had received interferon-based therapy for less than 12 weeks and previously discontinued from therapy due to toxicities associated with interferon or ribavirin. Patients who were null or partial responders to previous peginterferon/ribavirin or interferon-beta/ribavirin therapy were defined as never having attained an undetectable HCV RNA level after at least 12 weeks of therapy. Null responders included patients who never attained at least a 2-log10 decrease from baseline in HCV RNA levels at week 12, and partial responders never achieved undetectable HCV RNA levels after 12 weeks of therapy.
