Pharmacokinetic drug-drug interaction between the COVID-19 3CL protease inhibitor GST-HG171 and itraconazole in healthy subjects.

GST-HG171 (also known as atilotrelvir) is a novel, orally administered 3CL protease inhibitor approved in China for treating mild-to-moderate COVID-19. In this study, we assessed the drug-drug interaction between GST-HG171 (boosted with ritonavir) and itraconazole (a strong CYP3A inhibitor) in healthy Chinese adult volunteers. A total of 12 healthy subjects were enrolled in this two-period study. In period 1, all subjects received 150 mg GST-HG171/100 mg ritonavir twice daily (BID) on Days 1-3 (with a single dose on Day 3); after a 5-day washout period, subjects proceeded to period 2. In period 2, subjects orally took 200 mg itraconazole once daily (QD) on Days 8-16. On Days 12-14, subjects were co-administered 150 mg GST-HG171/100 mg ritonavir (BID, with a single dose on Day 14) and itraconazole. Serial blood samples were collected after administration of GST-HG171/ritonavir alone and co-administration of itraconazole for the measurement of pharmacokinetic parameters. Co-administration of itraconazole with GST-HG171/ritonavir resulted in a mild increase in the Cmax of GST-HG171 and ritonavir by approximately 8% and 28%, respectively, while systemic exposure (area under the plasma concentration-time curve [AUC]) was elevated by approximately 45% and 33%, respectively. There was no apparent increase in the incidence or severity of AEs during the co-administration period. In conclusion, co-administration of itraconazole, a strong CYP3A4 inhibitor, with GST-HG171/ritonavir resulted in a moderate increase in exposure of GST-HG171 and mild increase in exposure of ritonavir, and it had an acceptable safety profile and was well tolerated in this study.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT06087055.