1Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
2Buffalo Clinical Research Center, Buffalo, NY, USA.
3University Hospital Basel, Basel, Switzerland.
4PAREXEL International GmbH, Berlin, Germany.
5Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland.
6Boehringer Ingelheim Pharmaceuticals, Inc., Columbus, OH, USA.
7Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
8Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
9Boehringer Ingelheim Ltd., Burlington, ON, Canada.
Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. Studies were performed to investigate potential drug interactions between faldaprevir and commonly used antiretrovirals darunavir/ritonavir, efavirenz and tenofovir to guide the co-administration of faldaprevir with these agents in HIV/HCV co-infected patients.
In three open-label, phase I pharmacokinetic (PK) studies, healthy adult volunteers received: (i) darunavir/ritonavir (800 mg/100 mg once daily [QD]) with and without faldaprevir (240 mg QD); (ii) faldaprevir (240 mg twice daily [BID]) with and without efavirenz (600 mg QD); or (iii) faldaprevir (240 mg BID) or tenofovir (300 mg QD) alone and in combination. To assess potential drug interactions, geometric mean ratios and 90% confidence intervals for PK parameters were calculated. Safety was evaluated.
Efavirenz decreased faldaprevir AUC by 35%, Cmax by 28%, and Cmin by 46%, consistent with induction of CYP3A by efavirenz. Tenofovir decreased faldaprevir AUC by 22%, which was not considered clinically relevant. Faldaprevir had no clinically relevant effects on darunavir or tenofovir PK (15% and 22% AUC increase, respectively). Adverse events were consistent with the known safety profiles of faldaprevir and the antiretrovirals being examined.
No clinically significant interactions were observed between faldaprevir and darunavir/ritonavir or tenofovir. A potentially clinically relevant decrease in faldaprevir exposure was observed when co-administered with efavirenz; this decrease can be managed using the higher of the two faldaprevir doses tested in phase III trials (240 mg QD as opposed to 120 mg QD).