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Population Pharmacokinetics of Glecaprevir/Pibrentasvir in HCV‐infected Japanese Subjects in Phase 3 CERTAIN‐1 and CERTAIN‐2 Trials.
- Source :
- Journal of Clinical Pharmacology; Mar2020, Vol. 60 Issue 3, p331-339, 9p
- Publication Year :
- 2020
-
Abstract
- Glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (Mavyret/Maviret) is an all‐oral, pangenotypic, interferon‐ and ribavirin‐free combination regimen approved for the treatment of chronic hepatitis C virus (HCV) infection. The objective of the current analyses was to characterize the pharmacokinetics (PK) of GLE/PIB in HCV‐infected Japanese patients. Data from 332 subjects enrolled in 2 Japan phase 3 trials, CERTAIN‐1 and CERTAIN‐2, were used in the analyses. Pharmacokinetics of GLE/PIB were characterized using a nonlinear mixed‐effects modeling. The analyses evaluated the impact of covariates (concomitant medications and demographic and clinical covariates such as renal impairment, effect of cirrhotic status) on GLE/PIB PK. GLE and PIB PK were described by 1‐ and 2‐compartment models, respectively. Presence of cirrhosis, age, and body weight were identified as significant covariates on GLE/PIB PK. A trend toward higher GLE and PIB exposures in older patients and higher PIB exposures in heavier patients was observed; however, these increases were not considered clinically meaningful. GLE and PIB exposures were higher in HCV‐infected subjects with cirrhosis (Child‐Pugh A; GLE area under the plasma concentration–time curve was 160% higher, and PIB area under the plasma concentration–time curve was 21% higher) compared to subjects without cirrhosis. Renal function (including subjects with end‐stage renal disease with dialysis) had no impact on GLE or PIB exposures. The GLE/PIB dose was well tolerated in the Japanese population, and no dose adjustment is needed for the evaluated intrinsic and extrinsic factors. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00912700
- Volume :
- 60
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 141780171
- Full Text :
- https://doi.org/10.1002/jcph.1524