Glecaprevir/Pibrentasvir + Raltegravir = Unknown or no reaction

Study Design

This was a Phase 1, randomized, single-center, mutliple-dose (non-fasting) open label study to evaluate the pharmacokinetics (PK), tolerability and safety of the combination of ABT-493 + ABT-530 (DAA) when co-administered with rilpivirine (RPV).There were two cohorts for this study, each with 12 healthy participants.Cohort 1: ABT-493 + ABT-530 (300/120mg) once daily was administered on Days 1-7 alone (Period 1). This was followed by co-administration ofABT-493 + ABT-530 (300/120mg) plus RPV 25 mg once daily on Days 1-14 in Period 2.Cohort 2:RPV 25 mgonce daily was administered on Days 1-14 alone (Period 1).This was followed by co-administration ofABT-493 + ABT-530 (300/120mg) plus RPV 25 mg once daily on Days 1-7 in Period 2.

Study Results

PK ParameterDrug [Central Value Ratios and 90% Confidence Intervals]ABT-493ABT-530RALCmax0.94 [0.78, 1.12]1.01 [0.94, 1.07]1.34 [0.89, 1.98]AUCtau0.93 [0.84, 1.03]0.99 [0.92, 1.07]1.47 [1.15, 1.87]Ctrough1.02 [0.88, 1.18]0.97 [0.90, 1.04]2.64 [1.42, 4.91]Using central value ratios and 90% confidence intervals, following co-administration with RAL, ABT-493 and ABT-530 Cmax, AUC24and Ctroughwere minimally affected compared to administration of the DAA combination alone.Compared to RAL alone, co-administration with the DAAs increased RAL Cmax, AUC12 and C12 central values by 34%, 47% and 164%, respectively.No clinically significant vital signs, lab measurements, severe adverse events or new safety signalswere observed.

Study Conclusions

References

Oberoi RK, Kosloski MP, B Ding, et al. Interactions between abt-493 plus abt-530 combination and rilpivirine or raltegravir. Conference On Retroviruses And Opportunistic Infections. Boston, MA. ; 2016.

Study Design

In a sequential 2-periods, open label, single-center, phase I study, the pharmacokientic (PK) drug interaction potentail was assessed between GLE/PIB and RAL. Healthy adults age between 18 and 55 received GLE/PIB 300/120mg (n12) once daily in period 2 (days 1-10). These individuals also recevied raltegravir 400mg twice daily on period 1 (days 1-3) and period 2(day 1 and days 8-10). GLE/PIB blood sample were collected on period 2 days 1,7 and 10. Raltegravir sample were collected on period 1 day 3 and period 2 day 1 and 10.

Study Results

When coadministered with GLE/PIB, RAL exposures were higher (Cmax increased 34, AUC24 increased 47, and C12 increased to 2.6 fold) than for RAL alone. GLE and PIB exposures were similar (&8804;7 difference) with or without RAL.

Study Conclusions

There is no clinically significant interactions observed between GLE/PIB and RAL.

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.