Objective: Infection with hepatitis C virus is the leading indication for liver transplantation and most common cause of infectious disease-related mortality in the United States. BZF961 is a novel inhibitor of the hepatitis C virus NS3-4A protease. Methods: This sequential, three part exploratory first-in-human study investigated the safety and pharmacokinetics of single and multiple ascending oral doses of BZF961 in healthy subjects. The first two parts were randomized, double-blind, placebo-controlled, time-lagged, single and multiple ascending oral dose segments. The third part analyzed the effect of ritonavir on BZF961 pharmacokinetics. Results: BZF961 was generally safe and well-tolerated in single and multiple oral doses in healthy subjects. There were no deaths and no serious adverse events. The most common adverse events were nausea and other gastrointestinal symptoms. Co-administration of ritonavir with BZF961 was well tolerated and increased BZF961 exposure by up to 60-fold, as well as reduced the overall exposure variability. Conclusions: BZF961 was generally safe and well-tolerated and its exposure was boosted by the co-administration of ritonavir.
Keywords: BZF961; First-in-human; protease inhibitor; ritonavir.