1Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA firstname.lastname@example.org.
2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
3Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
4CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
5Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
6Boehringer Ingelheim Ltd/Ltée, Burlington, ON, Canada.
Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor with negligible urinary excretion. We assessed the pharmacokinetics and safety of a single oral dose of faldaprevir (480 mg) in 32 HCV-negative subjects with renal impairment or normal renal function. Compared with subjects with normal renal function, the adjusted geometric mean ratios (90% confidence interval) for overall exposure AUC0-∞ were 113.6% (41.6-310.2%), 178.3% (85.2-373.0%), and 169.2% (73.2-391.2%) for subjects with mild, moderate, or severe renal impairment, respectively. Overall, 5/8 (63%) subjects with normal renal function and 20/24 (83%) subjects with renal impairment reported adverse events, with gastrointestinal events being the most common. No severe or serious adverse events or deaths were reported. These results suggest that moderate or severe renal impairment can result in a modest increase in faldaprevir exposure. The increase in exposure may be related to decrease in the activity of the liver uptake transporter OATP1B1 as a result of renal impairment. Given this relatively slight increase in exposure, a dose adjustment in HCV patients with renal impairment is not warranted. (ClinicalTrials.gov registration number NCT01957657).