Population Pharmacokinetic Analysis of Ledipasvir/Sofosbuvir in Japanese Subjects with Chronic Genotype 1 HCV Infection

【Background】Pharmacokinetic (PK) data were collected from the Phase 3 study of Ledipasvir (LDV) and Sofosbuvir (SOF) ± ribavirin in GT1 HCV-infected Japanese subjects for Population PK analysis.
【Methods】166 treatment-naive and 175 previously-treated subjects were enrolled and all subjects received LDV/SOF ± ribavirin. Intensive PK (n = 23) and sparse PK (n =341) samples were collected to evaluate the pharmacokinetics of LDV and SOF in the Japanese subjects. Individual PK parameters were estimated for subjects using previously developed Population PK models for LDV, SOF and GS-331007. The effect of demographic variables on LDV, SOF and GS-331007 exposure was evaluated.
【Results】Population PK analysis estimated the mean (％CV) steady-state AUC_tau, C_max, and/or C_tau for LDV, SOF, and GS-331007. Compared to the historical data, LDV exposure was modestly higher in Japanese subjects and this increase was not considered clinically relevant. Sofosbuvir and GS-331007 exposures were comparable between the two populations with the exception of sofosbuvir C_max, which was slightly lower in Japanese subjects and not considered clinically relevant.
【Conclusion】The PK of SOF and GS-331007 in Japanese subjects was comparable to PK observed in historical studies. These data support the use of LDV/SOF for the treatment of GT1 HCV infection in Japanese patients.