There is no clinically significant interactions observed between GLE/PIB and EVG/c/FTC/TAF.
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide versus Glecaprevir/Pibrentasvir
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Study Design
An open label, multiple-dose study was conducted in healthy adult subjects receiving GLE 300 mg QD + PIB 120 mg QD with ELV/COBI/FTC/ TAF 150/150/200/10 mg QD (n=24, Arm 1) or ABC/DTG/3TC 600/50/300 mg QD (Arm 2, N=24) alone or in combination. Intensive pharmacokinetic assessments were performed for GLE, PIB, and anti-retroviral drugs on multiple days. Effects of GLE + PIB on the pharmacokinetics of the antiretroviral drugs and vice versa were assessed by a repeated-measures analysis using SAS. Safety was evaluated via assessment of adverse events, vital signs, ECGs and clinical laboratory tests.
Study Results
In Arm 1, Cmax and AUC were increased by 150% to 205% for GLE and by 24% to 57% for PIB, when co-administered with ELV/COBI/FTC/TAF. GLE + PIB increased Cmax and AUC of ELV and COBI by 29% to 47%, but not of FTC or tenofovir (≤ 12% change). In Arm 2, GLE and PIB Cmax and AUC were slightly lower (25% to 28%) when coadministered with ABC/DTG/3TC. Cmax and AUC of ABC, DTG, and 3TC were not impacted by GLE + PIB (≤ 13% difference). No clinically significant vital signs or laboratory measurements were observed during the study with the exception of one subject in Arm 1 who discontinued from the study due to a Grade 3 decrease in neutrophil count during ELV/COBI/FTC/ TAF and GLE-PIB coadministration.
Study Conclusions
Results from the study supported coadministration of GLE/PIB with these combination antiretroviral regimens in ongoing Phase 3 studies in HIV/HCV co-infected subjects. No dose-adjustment is required when GLE/PIB are coadministered with ELV, FTC, TAF, ABC, DTG, or 3TC.
References
Kosloski MP, Dutta S, Viani RM, Qi X, Trinh R, Campbell A, Liu W. Glecaprevir and pibrentasvir interactions with combination antiretroviral regimens [abstract]. Conference On Retroviruses And Opportunistic Infections. Seattle, WA, USA. 2017; February 2017.
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide versus Glecaprevir/Pibrentasvir
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Study Design
In a parallel 2-periods, open-label, single-center, phase I study, the pharmacokinetic (PK) drug interaction potential was assessed betweeen GLE/PIB and EVG/c/FTC/TAF. Healthy adults age between 18 and 55 recevied GLE 300mg/PIB 120mg (n7) once daily in period 1(Days 1-7). In period 2 (days 1-14), subjects recevied GLE/PIB with EVG/c/FTC/TAF 150/150/200/10mg once daily (n14). For assessment of the GLE/PIB plasma concentration, samples were collected on period 1 day 7 and 14, period 2 days 1 and 14 prior dosing. For EVG/c/FTC/TAF, samples were collected on period 2 days 1 and 14.
Study Results
When coadministered orally with GLE/PIB, FTC and tenofovir exposures were similar (&8804;25 difference), and EVG and cobicistat exposures were up to 72 higher compared to EVG/c/ FTC/TAF alone.GLE (Cmax increased to2.5-fold, AUC24 increased to 2.1-fold, and C24 increased to 4.6-fold) and PIB (AUC24 increased 57 and Ctrough increased 89) were also observed upon coadministration with EVG/c/FTC/TAF relative to GLE/PIB alone.
Study Conclusions
There is no clinically significant interactions observed between GLE/PIB and EVG/c/FTC/TAF.
References
Koloski MP, et al.. Drug-drug interactions of glecaprevir and pibrentasvir coadministered with human immunodeficiency virus antiretrovirals. Journal Of Infectious Diseases. 2020; 2: 223-31.
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