Effects of Renal Impairment and Hemodialysis on the Pharmacokinetics and Safety of the Glecaprevir and Pibrentasvir Combination in HCV-Negative Subjects [PublishAheadOfPrint]

Hepatitis C virus (HCV) infection is an independent risk factor for developing chronic renal impairment and end-stage renal disease. Limited treatment options are available for HCV genotypes 2, 3, 5, and 6 infection in patients with eGFR <30 mL/min. Glecaprevir and pibrentasvir are active against all six major HCV genotypes, primarily excreted in the bile, and have minimal renal elimination. Therefore, combined treatment with these direct-acting antivirals may be useful for patients with HCV infection and chronic kidney disease. A Phase 1, multicenter, open-label study evaluated the effects of renal impairment on the pharmacokinetics and safety of glecaprevir/pibrentasvir. In sub-study 1, 38 subjects with chronic kidney disease Stages 2 to 5 not on dialysis or with normal renal function received single doses of the glecaprevir 300 mg and pibrentasvir 120 mg combination. In sub-study 2, 8 subjects requiring hemodialysis received single doses of the glecaprevir 300 mg and pibrentasvir 120 mg combination under dialysis and non-dialysis conditions. Regression analyses demonstrated increased glecaprevir and pibrentasvir plasma exposure, as determined by area under the curve, with decreasing renal function up to 56% and 46%, respectively, in subjects with eGFR <15 mL/min/1.73 m². In dialysis-dependent subjects, glecaprevir and pibrentasvir exposures were similar (≤ 18% difference) when study drugs were administered before hemodialysis or on a non-dialysis day. Adverse events were mostly mild, the most common being self-limited fatigue (3 subjects). The study findings support clinical evaluation of glecaprevir/pibrentasvir without dose adjustment in HCV-infected subjects with renal impairment.

This study is registered at ClinicalTrials.gov: NCT 02442258.

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