1Research and Development, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ, 08543-4000, USA, email@example.com.
BACKGROUND AND OBJECTIVES:
The combination of direct-acting antiviral agents in patients with chronic hepatitis C virus (HCV) infection has demonstrated clinical benefit; however, evaluation of potential drug-drug interactions is required prior to therapy.
An open-label study assessed the pharmacokinetics and tolerability of the HCV NS5A replication complex inhibitor daclatasvir and the HCV NS3 protease inhibitor asunaprevir when co-administered in healthy subjects. Daclatasvir 60 mg once daily and asunaprevir 600 mg twice daily were dosed for 7 days alone followed by combination dosing for 14 days at 30 mg once daily and 200 mg twice daily, respectively. Further assessments were provided comparing exposures from the current study with those from studies in HCV-infected patients receiving either the same or higher doses of daclatasvir or asunaprevir administered alone or together.
Dose-normalized daclatasvir and asunaprevir morning exposures were comparable with control in healthy subjects, with geometric mean area under the concentration-time curve ratios of 1.202 (90 % CI 1.113-1.298) and 0.868 (90 % CI 0.726-1.038), respectively. In HCV patients daclatasvir and asunaprevir exposures were largely comparable, when administered together or alone.
Additional data support the conclusion that there is no clinically meaningful interaction between daclatasvir and asunaprevir in either healthy subjects or HCV-infected patients, including those also receiving peginterferon-α/ribavirin, and that the combination of daclatasvir 60 mg once daily and asunaprevir 200 mg twice daily is generally well-tolerated.