Viral Kinetic Study With Viramidine in Therapy-Naive Patients With Chronic Hepatitis C

• Efficacy: The proportion of patients with hepatitis C virus (HCV) RNA undetectable or with at least a 2-log drop from baseline at CT Week 4 in the viramidine pre-load group versus the viramidine standard dosing group.
• Safety: Evaluation of adverse events (AEs).
• Safety: Physical exams
• Safety: Vital signs
• Safety: Laboratory tests

• - Efficacy: The proportion of patients with hepatitis C virus (HCV) RNA undetectable or with at least a 2-log drop from baseline at CT Week 4 in the viramidine pre-load group versus the viramidine standard dosing group.
• - Safety: Evaluation of adverse events (AEs).
• - Safety: Physical exams
• - Safety: Vital signs
• - Safety: Laboratory tests

The purpose of this study is to examine the rapid virologic response (RVR) at combination therapy (CT) Week 4 between groups receiving a standard combination peginterferon alfa-2b/viramidine dosing regimen versus a cohort that receives 4 weeks of viramidine monotherapy prior to the start of peginterferon alfa-2b/viramidine combination therapy.

This Phase 2b multicenter study, which is being conducted solely in the United States, consists of a randomized, double-blind, monotherapy period, where patients will receive either viramidine or placebo for 4 weeks. After the monotherapy period, all patients will receive viramidine plus peginterferon alfa-2b combination therapy for 48 weeks in an open-label fashion and will then participate in a 24-week follow-up period after completion of combination therapy. The RVR at CT Week 4 between groups receiving a standard combination peginterferon alfa-2b/viramidine dosing regimen versus a cohort that receives 4 weeks of viramidine monotherapy prior to the start of peginterferon alfa-2b/viramidine combination therapy will be examined. The differences in virological response during treatment and end of follow-up between African-Americans and Caucasians (non-Hispanics), as well as a correlation between duration of viral negativity (DVN) and sustained virologic response (SVR) based on race and dosing regimen, will also be assessed.

• Drug: Viramidine
• Drug: Peginterferon alfa-2b

Inclusion Criteria:

• Treatment-naive, genotype 1 only, compensated, chronic hepatitis C infected Caucasian or African-American patients
• Body weight greater than 61 kg and not more than 87.3 kg
• HCV RNA greater than 2 million copies/mL
• Elevated measured or historical alanine aminotransferase
• Hemoglobin at least 12.0 g/dL for females and at least 13.0 g/dL for males
• Calculated creatinine clearance greater than 70 mL/min

Exclusion Criteria:

• Cirrhosis of the liver
• Alanine aminotransferase greater than 3 times the upper limit of normal
• Severe neuropsychiatric disorders
• History or clinical manifestations of significant metabolic, hematological, pulmonary, ischemic, or unstable heart disease, gastrointestinal, neurological, renal, urological, endocrine, ophthalmologic disorders including severe retinopathy, or immune mediated disease
• Other co-morbid chronic viral infections including hepatitis B and the human immunodeficiency virus (HIV)