Population Pharmacokinetics of Glecaprevir/Pibrentasvir in HCV‐infected Japanese Subjects in Phase 3 CERTAIN‐1 and CERTAIN‐2 Trials. (12th September 2019)

• Record Type: Journal Article
• Authors: Suleiman, Ahmed Abbas; Lin, Chih‐Wei; Liu, Wei; Eckert, Doerthe; Mensing, Sven; Burroughs, Margaret; Kato, Koji; Chayama, Kazuaki; Kumada, Hiromitsu; Oberoi, Rajneet K.
• Is Part Of: Journal of clinical pharmacology. Volume 60:Number 3(2020)
• Page Start: 331
• Page End: 339
• Publication Date: 2019-09-12
• Subjects: direct‐acting antivirals -- glecaprevir/pibrentasvir -- hepatitis C virus -- Japanese -- population pharmacokinetics; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.1524
• Languages: English
• ISSNs: 0091-2700

Abstract

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.