Fostemsavir + Ritonavir = Precautionary

Study Design

In an open-label, multiple-dose, four-sequence, crossover study, 36 healthy subjects were randomized 1:1:1:1 to receive one of four treatment sequences with three consecutive treatments: Sequence 1 (n=9): 9 healthy subjects received fostemsavir (formerly known as BMS-663068) 600 mg twice daily for 5 days (Days 1-5), followed by coadministration of fostemsavir 600 mg twice daily plus RTV 100 mg once daily for 10 days (Days 6-15). Subjects then received fostemsavir 600 mg twice daily, ATV 300 mg once daily, and RTV 100 mg once daily for 10 days (Days 16-25).Sequence 2 (n=9): 9 healthy subjects received fostemsavir at 600 mg twice daily for 5 days (Days 1-5). Subjects then received fostemsavir 600 mg twice daily, ATV 300 mg once daily, and RTV 100 mg once daily for 10 days (Days 6-15), followed by coadministration of fostemsavir 600 mg twice daily plus RTV 100 mg once daily for 10 days (Days 16-25). Sequence 3 (n=9): 9 healthy subjects received fostemsavir 600 mg twice daily for 5 days (Days 1-5), followed by coadministration of ATV 300 mg once daily plus RTV 100 mg once daily for 10 days (Days 6-15). Subjects then received fostemsavir 600 mg twice daily, ATV 300 mg once daily, and RTV 100 mg once daily for 10 days (Days 16-25).Sequence 4 (n=9): 9 healthy subjects received fostemsavir at 600 mg twice daily for 5 days (Days 1-5). Subjects then received fostemsavir 600 mg twice daily, ATV 300 mg once daily, and RTV 100 mg once daily for 10 days (Days 6-15), followed by coadministration of ATV 300 mg once daily plus RTV 100 mg once daily for 10 days (Days 16-25).Plasma samples for analysis of both temsavir (formerly known as BMS-626529; an active metabolite of prodrug, fostemsavir) and ATV/r were obtained predose and at 1, 2, 3, 4, 6, 8, and 12h postdose on Days 5, 15, and 25.

Study Results

Coadministration of fostemsavir and RTV increased temsavir AUC [90% CI] by 1.45-fold [1.29,1.61] and Cmax [90% CI] by 1.53-fold [1.31, 1.79] compared with administration of fostemsavir alone. However, coadministration of fostemsavir did not significantly impact exposure and plasma concentration of RTV. Geometric mean ratios (GMRs; fostemsavir + RTV / RTV) [90% CIs] of AUC and Cmax for RTV were 1.07 [1.03, 1.10] and 1.02 [0.957, 1.09], respectively.

Study Conclusions

References

Li Zhu, Matthew Hruska, Carey Hwang, Vaishali Shah, Michael Furlong, George J Hanna, Richard Bertz, Ishani Savant Landry. Pharmacokinetic interactions between bms-626529, the active moiety of the hiv-1 attachment inhibitor prodrug bms-663068, and ritonavir or ritonavir-boosted atazanavir in healthy subjects. Antimicrobial Agents And Chemotherapy. 2015; 7: 3816-3822.