A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

A Blinded, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

The purpose of this study was to assess the safety, tolerability, pharmacokinetics and antiviral activity of ABT-333 (also known as dasabuvir) in treatment-naïve, hepatitis C virus (HCV)-infected participants.

This was a Phase 2a, blinded, randomized, placebo-controlled clinical trial in hepatitis C virus (HCV)-infected adults with 2 planned sequential evaluations, Part 1 and Part 2. The study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-333 or placebo monotherapy, followed by 26 days of ABT-333 or placebo with pegylated interferon a-2a (pegIFN) and ribavirin (RBV) combination therapy. Review of safety and efficacy in Part 1 of the study showed similar response rates across ABT-333 doses so Part 2 of the study was not performed. The study also assessed emergence of resistant HCV in conjunction with kinetics of viral load decay and rebound in treatment-naïve, HCV-infected participants.

Inclusion Criteria:

• Participant has provided written consent.
• If female, participant is postmenopausal or surgically sterile.
• If male, must be practicing two effective methods of birth control.
• Participant is hepatitis C virus (HCV) genotype 1 with HCV ribonucleic acid levels >50,000 IU/mL.
• Participants must demonstrate chronic hepatitis C infection for at least 6 months prior to study enrollment.
• Participants must have a liver biopsy with histology consistent with HCV-induced liver damage, and with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV.
• Condition of general good health other then HCV infection.
• Participants with a history of thyroid disease must have a thyroid stimulating hormone (TSH) value in the normal range.

Exclusion Criteria:

• No prior history of receiving therapy for HCV infection.
• Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus antibody (HIV Ab).
• Pregnant or breastfeeding females or male partners of women who are pregnant.
• History of seizures or cancer.
• History of major depressive disorder within 2 years.
• Any current or past history of cirrhosis.
• Any cause of liver disease other than chronic HCV infection.