Fostemsavir + Atazanavir/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 ATV/r increased temsavir AUC [90% CI] by 1.54-fold [1.44,1.65] and Cmax [90% CI] by 1.68-fold [1.58, 1.79] compared with administration of fostemsavir alone. These moderate increases were not associated with any additional safety signals, according to the authors.Coadministration of fostemsavir did not significantly impact exposure and plasma concentration of ATV. Geometric mean ratios (GMRs; fostemsavir + ATV/r / ATV/r) [90% CIs] of AUC and Cmax for ATV were 1.09 [1.03, 1.15] and 1.03 [0.963, 1.10], 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.